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Hao L, Zhu L, Wang B, Xu J, Zhao X, Zhao J, Chen Z, Wang X. Predicting Benign and Malignant Subpleural Pulmonary Lesions With a Nomogram Model Using Clinical and B-Mode Ultrasound Parameters. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:1134-1142. [PMID: 40221224 DOI: 10.1016/j.ultrasmedbio.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 03/18/2025] [Accepted: 03/22/2025] [Indexed: 04/14/2025]
Abstract
OBJECTIVE To develop and validate an individualized nomogram for distinguishing between benign and malignant subpleural pulmonary lesions (SPLs) using B-mode ultrasound imaging and clinical data. METHODS A total of 425 patients with SPLs were enrolled and classified into two groups: 220 patients were diagnosed with malignant lesions, and 205 with benign lesions. Patients were randomly assigned to a development cohort (DC, n = 297) and a validation cohort (VC, n = 128) in a 7:3 ratio. Statistical analyses included rank-sum tests and chi-square tests. Boruta analysis was used to identify key features associated with malignant SPLs. The multivariable logistic regression model based on independent malignant SPL factors was developed and represented as a nomogram. The model's performance was assessed in terms of discrimination, calibration and clinical utility. RESULTS Six variables were selected to construct the nomogram: age, pack-year of smoking, air bronchogram, the angle between the lesion border and the thoracic wall, posterior echo of the lesion and visceral pleural invasion. The area under the receiver operating characteristic curve for the model was 0.859 (95% CI: 0.816-0.901) in the DC and 0.862 (95% CI: 0.800-0.923) in the VC. Calibration curve analysis demonstrated that the nomogram closely aligned with the ideal curve, reflecting its good calibration. Furthermore, decision curve analysis, clinical impact curve (CIC) and net reduction curve (NRC) further confirmed the model's favorable clinical utility. CONCLUSION We have developed a nomogram that serves as an effective tool for assessing malignant SPLs. This model holds significant promise as a complementary diagnostic aid, particularly in primary healthcare settings and bedside examination.
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Affiliation(s)
- Lei Hao
- Medical Imaging Department of Shanxi Medical University, Taiyuan, China; Departments of Ultrasound, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Lijing Zhu
- Departments of Ultrasound, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Bojuan Wang
- Departments of Ultrasound, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Jingzhu Xu
- Departments of Ultrasound, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Xin Zhao
- Departments of Ultrasound, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Jie Zhao
- Medical Imaging Department of Shanxi Medical University, Taiyuan, China
| | - Zezheng Chen
- Medical Imaging Department of Shanxi Medical University, Taiyuan, China
| | - Xinghua Wang
- Departments of Ultrasound, Second Hospital of Shanxi Medical University, Taiyuan, China.
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Kutlay C, Gülhan SŞE, Acar LN, Aslan M, Tanrıkulu FB. Impact of spread through air spaces (STAS) and lymphovascular invasion (LVI) on prognosis in NSCLC: a comprehensive pathological evaluation. Updates Surg 2025:10.1007/s13304-025-02170-9. [PMID: 40205081 DOI: 10.1007/s13304-025-02170-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 03/09/2025] [Indexed: 04/11/2025]
Affiliation(s)
- Can Kutlay
- Ankara Etlik City Hospital, Ankara, Turkey.
| | | | - Leyla Nesrin Acar
- Ankara Atatürk Sanatoryum Education and Research Hospital, Ankara, Turkey
| | - Muhyettin Aslan
- Ankara Atatürk Sanatoryum Education and Research Hospital, Ankara, Turkey
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Fu JY, Wen CT, Wu CF, Hsieh JCH, Chang PC, Hsieh MJ, Liu YH, Lin YJ, Chang SC, Wu CY. Integrating Pathologic Stage and Perioperative Circulating Tumor Cell Variations: Early Relapse Prediction Model for Resectable Non-Small Cell Lung Cancer. JCO Precis Oncol 2025; 9:e2400709. [PMID: 40294350 PMCID: PMC12052053 DOI: 10.1200/po-24-00709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 02/16/2025] [Accepted: 03/11/2025] [Indexed: 04/30/2025] Open
Abstract
PURPOSE The primary therapeutic objective for patients with resectable non-small cell lung cancer (NSCLC) is the prevention of disease relapse. This study aimed to examine the correlation between perioperative circulating tumor cell (CTC) variations and disease relapse. MATERIALS AND METHODS Ninety-nine patients with resectable NSCLC were enrolled and classified into cohort 0-1a and cohort 1b-4 on the basis of the presence of lymph node metastasis. CTC levels were measured, and their correlation with disease-free survival was analyzed. RESULTS In cohort 0-1a, patients with a CTC count difference between postoperative day 3 and postoperation of <2.75, and a difference between postoperative day 3 and postoperation day 1 of <-0.25, showed no disease relapse. In cohort 1b-4, patients with a CTC count difference between postoperative day 3 and postoperation ≥6.25 had the highest risk of relapse, with all patients experiencing relapse within 2 years. For those with a difference <6.25, most relapses were identified within 2 years postoperation. CONCLUSION The proposed relapse prediction model effectively identified patients with no risk for disease relapse in cohort 0-1a and those with the highest risk for relapse in cohort 1b-4. These results may assist physicians in focusing on and prescribing adjuvant treatment for patients with a higher relapse risk.
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Affiliation(s)
- Jui-Ying Fu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Tsung Wen
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, New Taipei Municipal Tu-Cheng Hospital, New Taipei City, Taiwan
| | - Ching-Feng Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Jason Chia-Hsun Hsieh
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Hematology-Oncology, Department of Internal Medicine, New Taipei Municipal Tu-Cheng Hospital, New Taipei City, Taiwan
| | - Po-Chun Chang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Ming-Ju Hsieh
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yen-Hen Liu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yu-Jr Lin
- Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan
| | - Shu-Chen Chang
- Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Yang Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
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Isgir BB, Kocaman G, Kahya Y, Ozakinci H, Elhan AH, Yuksel C. Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study. Updates Surg 2025; 77:201-208. [PMID: 39488820 DOI: 10.1007/s13304-024-02000-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 09/10/2024] [Indexed: 11/04/2024]
Abstract
Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6 years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.
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Affiliation(s)
- Betul Bahar Isgir
- Department of Thoracic Surgery, Ankara University, 06230, Ankara, Turkey.
| | - Gokhan Kocaman
- Department of Thoracic Surgery, Ankara University, 06230, Ankara, Turkey
| | - Yusuf Kahya
- Department of Thoracic Surgery, Ankara University, 06230, Ankara, Turkey
| | - Hilal Ozakinci
- Department of Pathology, Ankara University, 06230, Ankara, Turkey
- Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, USA
| | | | - Cabir Yuksel
- Department of Thoracic Surgery, Ankara University, 06230, Ankara, Turkey
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Hashinokuchi A, Akamine T, Toyokawa G, Matsudo K, Nagano T, Kinoshita F, Kohno M, Tomonaga T, Kohashi K, Shimokawa M, Oda Y, Takenaka T, Yoshizumi T. Impact of the distance of spread through air spaces in non-small cell lung cancer. INTERDISCIPLINARY CARDIOVASCULAR AND THORACIC SURGERY 2024; 40:ivae181. [PMID: 39705189 PMCID: PMC11669314 DOI: 10.1093/icvts/ivae181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 12/05/2024] [Indexed: 12/22/2024]
Abstract
OBJECTIVES Spread through air spaces (STAS) is considered a poor prognostic factor in patients with resected non-small lung cell cancer; however, the clinical significance of STAS extent remains unclear. We hypothesized that the further the tumour cells spread from the tumour edge, the worse the prognosis becomes. METHODS This study retrospectively reviewed the data of 642 patients with completely resected pathological stage I-III non-small lung cell cancer between 2008 and 2018. The maximum spread distance (MSD) from the tumour edge to the farthest STAS was quantitatively evaluated, and STAS was categorized as limited (MSD ≤1000 μm) or extended (MSD >1000 μm), based on the median MSD. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS classification. RESULTS Patients were classified into STAS-negative (n = 382, 59.6%), limited STAS (n = 130, 20.2%) and extended STAS (n = 130, 20.2%) groups. Extended STAS was associated with a high maximum standardized uptake value, advanced pathological stage and vascular invasion compared with limited STAS. The extended STAS group demonstrated significantly shorter RFS and OS than both the limited STAS and STAS-negative groups (both P < 0.001 for RFS; P = 0.007 and P < 0.001 for OS, respectively). Multivariable analysis showed that extended STAS was an independent prognostic factor for both RFS and OS (P < 0.001, P < 0.001, respectively). CONCLUSIONS The distance from tumour edge to STAS affects prognosis in patients with completely resected non-small lung cell cancer. CLINICAL REGISTRATION NUMBER IRB approval number: 2019-232.
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Affiliation(s)
- Asato Hashinokuchi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takaki Akamine
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Gouji Toyokawa
- Department of Thoracic Surgery, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Chuo-ku, Fukuoka, Japan
| | - Kyoto Matsudo
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Taichi Nagano
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Fumihiko Kinoshita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mikihiro Kohno
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takumi Tomonaga
- Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Kohashi
- Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Mototsugu Shimokawa
- Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Yoshinao Oda
- Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoyoshi Takenaka
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Matsuoka S, Eguchi T, Iwaya M, Seshimoto M, Mishima S, Hara D, Kumeda H, Miura K, Hamanaka K, Uehara T, Shimizu K. Prognostic significance of immune-cell distribution and tumoral spread through air spaces - Multiplex spatial immunophenotyping analysis. Heliyon 2024; 10:e37412. [PMID: 39296057 PMCID: PMC11408789 DOI: 10.1016/j.heliyon.2024.e37412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 09/21/2024] Open
Abstract
Objectives Spread through air spaces (STAS) is a form of lung cancer invasion that extends beyond the tumor edge and is associated with a worse prognosis. Recent advances in immunotherapy highlight the importance of understanding the tumor microenvironment. This study aimed to investigate the prognostic significance of immune-cell distribution in lung cancer, focusing on the association with STAS. Materials and methods We retrospectively analyzed 283 patients who underwent curative-intent lung resection for primary lung cancer. Multiplex immunofluorescence staining/phenotyping was performed on tissue microarrays to assess the distribution of CD4, CD8, CD20, CD68, and FoxP3 immune cells within the center and tumor edge. We defined the delta-Edge value (Δ) as the difference in the number of immune cells between the tumor edge and center. Recurrence-free probability (RFP) was analyzed using Kaplan-Meier and Cox proportional hazard models. Results High ΔCD4 and ΔCD8 values were significantly associated with worse RFP. In stage I adenocarcinoma patients, STAS, and high ΔCD8 were independent risk factors for recurrence. Effect modification analysis revealed that high ΔFoxP3 was significantly associated with worse RFP in patients with STAS, but not in those without STAS. Patients with STAS and high Δimmune cell values had the lowest RFP among all groups. Conclusion Immune-cell distribution, particularly CD4, CD8, and FoxP3, is a crucial prognostic factor in lung cancer. STAS and specific immune cell distribution patterns can be used to further stratify patient prognosis. Understanding these interactions may provide insights into potential therapeutic targets for personalized lung cancer treatment.
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Affiliation(s)
- Shunichiro Matsuoka
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takashi Eguchi
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Mai Iwaya
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Maho Seshimoto
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shuji Mishima
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Daisuke Hara
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hirotaka Kumeda
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Kentaro Miura
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Kazutoshi Hamanaka
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Kimihiro Shimizu
- Division of General Thoracic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
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Wang Q, Song X, Zhang Y, Liang S, Zhang M, Wang H, Feng Y, Li R, Ding H, Chen Y, Xia W, Dong G, Xu L, Mao Q, Jiang F. A pro-metastatic tRNA fragment drives aldolase A oligomerization to enhance aerobic glycolysis in lung adenocarcinoma. Cell Rep 2024; 43:114550. [PMID: 39058593 DOI: 10.1016/j.celrep.2024.114550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/19/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Despite being the leading cause of lung cancer-related deaths, the underlying molecular mechanisms driving metastasis progression are still not fully understood. Transfer RNA-derived fragments (tRFs) have been implicated in various biological processes in cancer. However, the role of tRFs in lung adenocarcinoma (LUAD) remains unclear. Our study identified a tRF, tRF-Val-CAC-024, associated with the high-risk component of LUAD, through validation using 3 cohorts. Our findings demonstrated that tRF-Val-CAC-024 acts as an oncogene in LUAD. Mechanistically, tRF-Val-CAC-024 was revealed to bind to aldolase A (ALDOA) dependent on Q125/E224 and promote the oligomerization of ALDOA, resulting in increased enzyme activity and enhanced aerobic glycolysis in LUAD cells. Additionally, we provide preliminary evidence of its potential clinical value by investigating the therapeutic effects of tRF-Val-CAC-024 antagomir-loaded lipid nanoparticles (LNPs) in cell-line-derived xenograft models. These results could enhance our understanding of the regulatory mechanisms of tRFs in LUAD and provide a potential therapeutic target.
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Affiliation(s)
- Qinglin Wang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Xuming Song
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Yijian Zhang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Si Liang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Minhao Zhang
- Department of Anesthesiology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, No. 42, Baiziting, Nanjing 210000, Jiangsu, China
| | - Hui Wang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Yipeng Feng
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Rutao Li
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Hanlin Ding
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Yuzhong Chen
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Wenjie Xia
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Gaochao Dong
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China
| | - Lin Xu
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China.
| | - Qixing Mao
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China.
| | - Feng Jiang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, China.
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Kiemen AL, Almagro-Pérez C, Matos V, Forjaz A, Braxton AM, Dequiedt L, Parksong J, Cannon CD, Yuan X, Shin SM, Babu JM, Thompson ED, Cornish TC, Ho WJ, Wood LD, Wu PH, Barrutia AM, Hruban RH, Wirtz D. 3D histology reveals that immune response to pancreatic precancers is heterogeneous and depends on global pancreas structure. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.03.606493. [PMID: 39149369 PMCID: PMC11326156 DOI: 10.1101/2024.08.03.606493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer for which few effective therapies exist. Immunotherapies specifically are ineffective in pancreatic cancer, in part due to its unique stromal and immune microenvironment. Pancreatic intraepithelial neoplasia, or PanIN, is the main precursor lesion to PDAC. Recently it was discovered that PanINs are remarkably abundant in the grossly normal pancreas, suggesting that the vast majority will never progress to cancer. Here, through construction of 48 samples of cm3-sized human pancreas tissue, we profiled the immune microenvironment of 1,476 PanINs in 3D and at single-cell resolution to better understand the early evolution of the pancreatic tumor microenvironment and to determine how inflammation may play a role in cancer progression. We found that bulk pancreatic inflammation strongly correlates to PanIN cell fraction. We found that the immune response around PanINs is highly heterogeneous, with distinct immune hotspots and cold spots that appear and disappear in a span of tens of microns. Immune hotspots generally mark locations of higher grade of dysplasia or locations near acinar atrophy. The immune composition at these hotspots is dominated by naïve, cytotoxic, and regulatory T cells, cancer associated fibroblasts, and tumor associated macrophages, with little similarity to the immune composition around less-inflamed PanINs. By mapping FOXP3+ cells in 3D, we found that regulatory T cells are present at higher density in larger PanIN lesions compared to smaller PanINs, suggesting that the early initiation of PanINs may not exhibit an immunosuppressive response. This analysis demonstrates that while PanINs are common in the pancreases of most individuals, inflammation may play a pivotal role, both at the bulk and the microscopic scale, in demarcating regions of significance in cancer progression.
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Affiliation(s)
- Ashley L. Kiemen
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
- Institute for NanoBioTechnology, Johns Hopkins University
- Department of Functional Anatomy & Evolution, Johns Hopkins School of Medicine, Baltimore, MD
| | - Cristina Almagro-Pérez
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
- Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid, Leganés, Spain
| | - Valentina Matos
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
- Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid, Leganés, Spain
| | - Andre Forjaz
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
| | - Alicia M. Braxton
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Lucie Dequiedt
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
| | - Jeeun Parksong
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Courtney D. Cannon
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Xuan Yuan
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Sarah M. Shin
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Jaanvi Mahesh Babu
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Elizabeth D. Thompson
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Toby C. Cornish
- Department of Pathology and Data Science Institute, Medical College of Wisconsin, Milwaukee, WI
| | - Won Jin Ho
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Laura D. Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Pei-Hsun Wu
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
- Institute for NanoBioTechnology, Johns Hopkins University
| | - Arrate Muñoz Barrutia
- Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid, Leganés, Spain
- Bioengineering Division, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Ralph H. Hruban
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Denis Wirtz
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
- Institute for NanoBioTechnology, Johns Hopkins University
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9
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Meng Y, Wang Y, Liu L, Wu R, Zhang Q, Chen Z, Yao Y, Li X, Gong Y, Li H, Wang Z, Liu H. Immunohistochemistry identifies E-cadherin, N-cadherin and focal adhesion kinase (FAK) as predictors of stage I non-small cell lung carcinoma spread through the air spaces (STAS), and the combinations as prognostic factors. Transl Lung Cancer Res 2024; 13:1450-1462. [PMID: 39118895 PMCID: PMC11304152 DOI: 10.21037/tlcr-24-247] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 06/11/2024] [Indexed: 08/10/2024]
Abstract
Background Spread through air spaces (STAS) is one of the multiple modes of lung cancer dissemination, yet its molecular and clinicopathological characterization remains poorly studied. This study aimed to investigate the effect of adhesion molecule expression levels on the incidence of STAS and postoperative recurrence in stage I lung cancer patients undergoing radical resection. Methods E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed retrospectively using immunohistochemistry in patients undergoing radical resection for stage I non-small cell lung cancer (NSCLC). Patients were categorized into four groups based on adhesion molecule expression levels: "low/low", "high/low", "low/high", and "high/high", and the group with the lowest recurrence-free probability (RFP) was defined as high risk. Associations between those adhesion molecules' expression levels and STAS were determined by using the Chi-squared test and logistic regression model. RFP was analyzed by using the log-rank test and Cox proportional risk model. Results As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All 60 patients' tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive (n=30) and STAS-negative (n=30) in baseline clinicopathologic features, except for histological growth patterns. We found that low expression of E-cadherin, high expression of N-cadherin and FAK, and males were independent predictors of higher incidence of STAS. Multivariate Cox analysis showed that tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/high FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. In addition, females and high N-cadherin/high FAK were associated with a high risk of recurrence in patients with STAS. Conclusions E-cadherin, N-cadherin, and FAK are predictors of STAS occurrence in stage I NSCLC, and their combinations are prognostic factors. The discovery of these molecular markers provides clinicians with a reliable means that may help in the early identification of individuals with a higher risk of recurrence in lung cancer patients, targeting personalized treatment plans such as aggressive adjuvant therapy or closer follow-up.
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Affiliation(s)
- Yunchang Meng
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China
| | - Yimin Wang
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China
| | - Leilei Liu
- Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Ranpu Wu
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Southeast University School of Medicine, Nanjing, China
| | - Qingfeng Zhang
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhangxuan Chen
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yang Yao
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Xinjing Li
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanzhuo Gong
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Huijuan Li
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhaofeng Wang
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Hongbing Liu
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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10
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Chen S, Hu T, Zhao J, Zhu Q, Wang J, Huang Z, Xiang C, Zhao R, Zhu C, Lu S, Han Y. Novel molecular subtypes of METex14 non-small cell lung cancer with distinct biological and clinical significance. NPJ Precis Oncol 2024; 8:159. [PMID: 39060379 PMCID: PMC11282101 DOI: 10.1038/s41698-024-00642-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Not all MET exon 14 skipping (METex14) NSCLC patients benefited from MET inhibitors. We hypothesized an inter-tumoral heterogeneity in METex14 NSCLC. Investigations at genomic and transcriptomic level were conducted in METex14 NSCLC samples from stage I-III and recurrent/metastatic patients as discovery and validation cohort. Four molecular subtypes were discovered. MET-Driven subtype, with the worst prognosis, displayed MET overexpression, enrichment of MET-related pathways, and higher infiltration of fibroblast and regulatory T cells. Immune-Activated subtype having the most idea long-term survival, had higher tertiary lymphoid structures, spatial co-option of PD-L1+ cancer cells, and GZMK+ CD8+ T cell. FGFR- and Bypass-Activated subtypes displayed FGFR2 overexpression and enrichments of multiple oncogenic pathways respectively. In the validation cohort, patients with MET-Driven subtype had better response to MET inhibitors than those with MET overexpression. Thus, molecular subtypes of METex14 NSCLC with distinct biological and clinical significance may indicate more precise therapeutic strategies for METex14 NSCLC patients.
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Affiliation(s)
- Shengnan Chen
- Department of Pathology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Tao Hu
- Department of Medicine, Amoy Diagnostics Co., Ltd., Xiamen, China
| | - Jikai Zhao
- Department of Pathology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Qian Zhu
- Department of Pathology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jin Wang
- Department of Medicine, Amoy Diagnostics Co., Ltd., Xiamen, China
| | - Zhan Huang
- Department of Medicine, Amoy Diagnostics Co., Ltd., Xiamen, China
| | - Chan Xiang
- Department of Pathology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ruiying Zhao
- Department of Pathology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Changbin Zhu
- Department of Medicine, Amoy Diagnostics Co., Ltd., Xiamen, China.
| | - Shun Lu
- Department of Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
| | - Yuchen Han
- Department of Pathology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
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11
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Chen M, Ding L, Deng S, Li J, Li X, Jian M, Xu Y, Chen Z, Yan C. Differentiating the Invasiveness of Lung Adenocarcinoma Manifesting as Ground Glass Nodules: Combination of Dual-energy CT Parameters and Quantitative-semantic Features. Acad Radiol 2024; 31:2962-2972. [PMID: 38508939 DOI: 10.1016/j.acra.2024.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/30/2024] [Accepted: 02/07/2024] [Indexed: 03/22/2024]
Abstract
RATIONALE AND OBJECTIVES To evaluate the diagnostic performance of dual-energy CT (DECT) parameters and quantitative-semantic features for differentiating the invasiveness of lung adenocarcinoma manifesting as ground glass nodules (GGNs). MATERIALS AND METHODS Between June 2022 and September 2023, 69 patients with 74 surgically resected GGNs who underwent DECT examinations were included. CT numbers on virtual monochromatic images were calculated at 40-130 keV generated from DECT. Quantitative morphological measurements and semantic features were evaluated on unenhanced CT images and compared between pathologically confirmed adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA) and invasive lung adenocarcinoma (IAC). Multivariable logistic regression analysis was used to identify independent predictors. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC) and compared using DeLong's test. RESULTS Monochromatic CT numbers at 40-130 keV were significantly higher in IAC than in AIS-MIA (all P < 0.05). Multivariate logistic analysis revealed that CT number of 130 keV (odds ratio [OR] = 1.02, P = 0.013), maximum cross-sectional long diameter (OR =1.40, P = 0.014), deep or moderate lobulation sign (OR =19.88, P = 0.005), and abnormal intranodular vessel morphology (OR = 25.57, P = 0.017) were independent predictors of IAC. The combined prediction model showed a favorable differentiation performance with an AUC of 0.966 (95.2% sensitivity, 94.3% specificity, 94.8% accuracy), which was significantly higher than that for each risk factor (AUC = 0.791-0.822, all P < 0.05). CONCLUSION A multi-parameter combined prediction model integrating monochromatic CT numbers from DECT and quantitative-semantic features is promising for the preoperative discrimination of IAC and AIS-MIA in GGN-predominant lung adenocarcinoma.
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Affiliation(s)
- Mingwang Chen
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Li Ding
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Shuting Deng
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Jingxu Li
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
| | - Xiaomei Li
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Mingjue Jian
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Yikai Xu
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Zhao Chen
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Chenggong Yan
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Lee JH, Kang Y, Kim S, Jung Y, Chung JH, Lee S, Yi E. Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma. Cancers (Basel) 2024; 16:2218. [PMID: 38927923 PMCID: PMC11201625 DOI: 10.3390/cancers16122218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.
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Affiliation(s)
- Jeong Hyeon Lee
- Department of Pathology, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (J.H.L.); (Y.K.); (S.K.)
| | - Younggjn Kang
- Department of Pathology, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (J.H.L.); (Y.K.); (S.K.)
| | - Seojin Kim
- Department of Pathology, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (J.H.L.); (Y.K.); (S.K.)
| | - Youggi Jung
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (Y.J.); (J.H.C.)
| | - Jae Ho Chung
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (Y.J.); (J.H.C.)
| | - Sungho Lee
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (Y.J.); (J.H.C.)
| | - Eunjue Yi
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul 02841, Republic of Korea; (Y.J.); (J.H.C.)
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13
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Kurz A, Müller H, Kather JN, Schneider L, Bucher TC, Brinker TJ. 3-Dimensional Reconstruction From Histopathological Sections: A Systematic Review. J Transl Med 2024; 104:102049. [PMID: 38513977 DOI: 10.1016/j.labinv.2024.102049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 02/18/2024] [Accepted: 03/14/2024] [Indexed: 03/23/2024] Open
Abstract
Although pathological tissue analysis is typically performed on single 2-dimensional (2D) histologic reference slides, 3-dimensional (3D) reconstruction from a sequence of histologic sections could provide novel opportunities for spatial analysis of the extracted tissue. In this review, we analyze recent works published after 2018 and report information on the extracted tissue types, the section thickness, and the number of sections used for reconstruction. By analyzing the technological requirements for 3D reconstruction, we observe that software tools exist, both free and commercial, which include the functionality to perform 3D reconstruction from a sequence of histologic images. Through the analysis of the most recent works, we provide an overview of the workflows and tools that are currently used for 3D reconstruction from histologic sections and address points for future work, such as a missing common file format or computer-aided analysis of the reconstructed model.
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Affiliation(s)
- Alexander Kurz
- Digital Biomarkers for Oncology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Heimo Müller
- Diagnostics and Research Institute for Pathology, Medical University of Graz, Graz, Austria
| | - Jakob N Kather
- Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany
| | - Lucas Schneider
- Digital Biomarkers for Oncology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tabea C Bucher
- Digital Biomarkers for Oncology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Titus J Brinker
- Digital Biomarkers for Oncology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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14
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Senchukova MA, Kalinin EA, Volchenko NN. Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance. World J Clin Oncol 2024; 15:614-634. [PMID: 38835849 PMCID: PMC11145955 DOI: 10.5306/wjco.v15.i5.614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/12/2024] [Accepted: 03/28/2024] [Indexed: 05/21/2024] Open
Abstract
BACKGROUND Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood. AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC). METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance. RESULTS Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083). CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
| | - Evgeniy A Kalinin
- Department of Thoracic Surgery, Orenburg Regional Cancer Clinic, Orenburg 460021, Russia
| | - Nadezhda N Volchenko
- Department of Pathology, PA Hertzen Moscow Oncology Research Centre, Branch of National Medical Research Radiological Center, Moscow 125284, Russia
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15
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Song AH, Williams M, Williamson DFK, Chow SSL, Jaume G, Gao G, Zhang A, Chen B, Baras AS, Serafin R, Colling R, Downes MR, Farré X, Humphrey P, Verrill C, True LD, Parwani AV, Liu JTC, Mahmood F. Analysis of 3D pathology samples using weakly supervised AI. Cell 2024; 187:2502-2520.e17. [PMID: 38729110 PMCID: PMC11168832 DOI: 10.1016/j.cell.2024.03.035] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 01/15/2024] [Accepted: 03/25/2024] [Indexed: 05/12/2024]
Abstract
Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.
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Affiliation(s)
- Andrew H Song
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Mane Williams
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
| | - Drew F K Williamson
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Sarah S L Chow
- Department of Mechanical Engineering, Bioengineering, and Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA
| | - Guillaume Jaume
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Gan Gao
- Department of Mechanical Engineering, Bioengineering, and Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA
| | - Andrew Zhang
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Bowen Chen
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Alexander S Baras
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Robert Serafin
- Department of Mechanical Engineering, Bioengineering, and Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA
| | - Richard Colling
- Nuffield Department of Surgical Sciences, University of Oxford, UK; Department of Cellular Pathology, Oxford University Hospitals NHS Foundations Trust, John Radcliffe Hospital, Oxford, UK
| | - Michelle R Downes
- Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Xavier Farré
- Public Health Agency of Catalonia, Lleida, Spain
| | - Peter Humphrey
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Clare Verrill
- Nuffield Department of Surgical Sciences, University of Oxford, UK; Department of Cellular Pathology, Oxford University Hospitals NHS Foundations Trust, John Radcliffe Hospital, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Lawrence D True
- Department of Laboratory Medicine & Pathology, University of Washington School of Medicine, Seattle, WA, USA
| | - Anil V Parwani
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | - Jonathan T C Liu
- Department of Mechanical Engineering, Bioengineering, and Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA.
| | - Faisal Mahmood
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA.
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16
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Li Y, Adusumilli PS, Chou TY, Kadota K, Mino-Kenudson M, Papotti M, Rekhtman N, Yagi Y, Yatabe Y, Travis WD. Pro: "Is Spread Through Air Spaces an In Vivo Phenomenon or an Inducible Artifact?". J Thorac Oncol 2024; 19:677-697. [PMID: 38719424 DOI: 10.1016/j.jtho.2024.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/26/2024] [Accepted: 03/01/2024] [Indexed: 04/06/2025]
Abstract
In this PRO-CON debate, you will read very different perspectives about a simple question regarding an observation under the microscope: What is the significance of tumor cells in the air spaces of the lung parenchyma beyond the tumor edge of a resected lung cancer? An important underlying question is whether this entire PRO-CON debate is a mere academic exercise or whether spread through air spaces (STAS), as currently defined, describes a clinically useful phenomenon. The journey of STAS began with a complete paradigm shift to reverse the thinking that all air space tumor cells beyond the edge of lung cancers are an artifact. This led to a new concept where STAS could be separated from artifacts with a definition that has proven to be clinically useful. As with any major change in thinking, it is understandable that there would be some disagreement with this paradigm shift. Nevertheless, after a decade since it was described, many pathologists and clinicians around the world have found STAS to provide important information about the behavior of lung cancer. Numerous PRO-STAS articles supporting the usefulness of STAS have been published with clinical data on many thousands of patients from numerous institutions all over the world. In contrast, for the CON-STAS articles, widespread international representation and data are limited. It is now difficult to ignore the numerous reports and is reasonable to consider how to use the presence of STAS in clinical decisions. Hopefully, this PRO-CON debate will further stimulate clinical and scientific investigations aimed at a better understanding of STAS.
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Affiliation(s)
- Yan Li
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People's Republic of China
| | - Prasad S Adusumilli
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Teh-Ying Chou
- Department of Pathology and Precision Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Kyuichi Kadota
- Molecular Oncologic Pathology, Department of Pathology and Host Defense, Kagawa University, Kagawa, Japan
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Mauro Papotti
- Department of Oncology, University of Turin, Turin, Italy
| | - Natasha Rekhtman
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Yukako Yagi
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Yasushi Yatabe
- Department of Pathology, National Cancer Center, Tokyo, Japan
| | - William D Travis
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
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Chen X, Zhou H, Wu M, Xu M, Li T, Wang J, Sun X, Tsutani Y, Xie M. Prognostic impact of spread through air spaces in patients with ≤2 cm stage IA lung adenocarcinoma. J Thorac Dis 2024; 16:2432-2442. [PMID: 38738220 PMCID: PMC11087609 DOI: 10.21037/jtd-24-444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 04/17/2024] [Indexed: 05/14/2024]
Abstract
Background In 2015, the World Health Organization (WHO) included spread through air space (STAS) as a new invasive mode of lung cancer. As a new mode of lung cancer dissemination, STAS has a significant and negative impact on patient prognosis. The surgical approach as well as lymph node dissection (LND) for STAS-positive patients is currently unclear. The aim of this study was to investigate the impact of different surgical approaches to STAS and LND on the prognosis of patients with ≤2 cm stage IA lung adenocarcinoma (LUAD). This study also investigated the possible relationship between STAS and the micropapillary histological subtype and its impact on patient prognosis. Methods A total of 212 patients with LUAD were included in this study from January 2016 to December 2017, and the overall survival (OS) of the patients was compared. The chi-square test and t-test were applied to compare the clinicopathological data of the patients, and the Cox model was used for the multivariate survival analysis. Results Of the 212 patients, 93 (43.9%) were STAS positive. The univariate analysis showed that the surgical approach, LND type, micropapillary pattern (MP), solid pattern, and STAS were risk factors for OS. The multivariate analysis showed that the surgical approach, MP, and STAS were risk factors for OS. The STAS-positive patients who underwent lobectomy had a better prognosis than those who underwent sublobar resection; however, there was no significant difference between the two surgical procedures in the STAS-negative group. Additionally, the STAS-positive patients who underwent systematic lymph node dissection (SLND) had a better prognosis than those who underwent limited lymph node dissection (LLND); however, there was no significant difference between the two LNDs in the STAS-negative group. Conclusions STAS plays an important role in patient prognosis and is an independent risk factor for OS of patients with ≤2 cm stage IA LUAD. When STAS is positive, the choice of lobectomy with SLND may result in a better long-term prognosis for patients.
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Affiliation(s)
- Xiao Chen
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Hangcheng Zhou
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China
| | - Mingsheng Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Meiqing Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Tian Li
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Jun Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Xiaohui Sun
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Yasuhiro Tsutani
- Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Mingran Xie
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
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Zeng J, Cheng Y, Xie W, Lin X, Ding C, Xu H, Cui B, Chen Y, Gao S, Zhang S, Liu K, Lu Y, Zhou J, Shi Z, Sun Y. Calcium-sensing receptor and NF-κB pathways in TN breast cancer contribute to cancer-induced cardiomyocyte damage via activating neutrophil extracellular traps formation. Cell Mol Life Sci 2024; 81:19. [PMID: 38196005 PMCID: PMC11073098 DOI: 10.1007/s00018-023-05051-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 10/26/2023] [Accepted: 10/28/2023] [Indexed: 01/11/2024]
Abstract
Cardiovascular disorders are commonly prevalent in cancer patients, yet the mechanistic link between them remains poorly understood. Because neutrophil extracellular traps (NETs) have implications not just in cardiovascular diseases (CVD), but also in breast cancer (BC), it was hypothesized to contribute to CVD in the context of oncogenesis. We established a mouse model using nude mice to simulate liver metastasis of triple-negative BC (TNBC) through the injection of MDA-MB-231 cells. Multiple imaging and analysis techniques were employed to assess the cardiac function and structure, including echocardiography, HE staining, Masson staining, and transmission electron microscopy (TEM). MDA-MB-231 cells underwent treatment with a CaSR inhibitor, CaSR agonist, and NF-κB channel blocker. The phosphorylation of NF-κB channel protein p65 and the expression and secretion of IL-8 were assessed using qRT-PCR, Western Blot, and ELISA, respectively. In addition, MDA-MB-231 cells were co-cultured with polymorphonuclear neutrophils (PMN) under varying conditions. The co-localization of PMN extracellular myeloperoxidase (MPO) and DNA were observed by cellular immunofluorescence staining to identify the formation of NETs. Then, the cardiomyocytes were co-cultured with the above medium that contains NETs or not, respectively; the effects of NETs on cardiomyocytes apoptosis were perceived by flow cytometry. The ultrastructural changes of myocardial cells were perceived by TEM, and ELISA detected the levels of myocardial enzyme (LDH, MDA and SOD). Overall, according to our research, CaSR has been found to have a regulatory role in IL-8 secretion in MDA-MB-231 cells, as well as in the formation of NETs by PMN cells. These findings suggest CaSR-mediated stimulation in PMN can lead to increased NETs formation and subsequently to cytotoxicity in cardiomyocytes, which potentially via activation of the NF-κB signaling cascade of BC cell.
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Affiliation(s)
- Jingya Zeng
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yangyang Cheng
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Wanlin Xie
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Xin Lin
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Chenglong Ding
- Department of Pathology, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154003, Heilongjiang, China
| | - Huimin Xu
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Baohong Cui
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yixin Chen
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Song Gao
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Siwen Zhang
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Kaiyue Liu
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yue Lu
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Jialing Zhou
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Zhongxiang Shi
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yihua Sun
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
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Willner J, Narula N, Moreira AL. Updates on lung adenocarcinoma: invasive size, grading and STAS. Histopathology 2024; 84:6-17. [PMID: 37872108 DOI: 10.1111/his.15077] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/25/2023]
Abstract
Advancements in the classification of lung adenocarcinoma have resulted in significant changes in pathological reporting. The eighth edition of the tumour-node-metastasis (TNM) staging guidelines calls for the use of invasive size in staging in place of total tumour size. This shift improves prognostic stratification and requires a more nuanced approach to tumour measurements in challenging situations. Similarly, the adoption of new grading criteria based on the predominant and highest-grade pattern proposed by the International Association for the Study of Lung Cancer (IASLC) shows improved prognostication, and therefore clinical utility, relative to previous grading systems. Spread through airspaces (STAS) is a form of tumour invasion involving tumour cells spreading through the airspaces, which has been highly researched in recent years. This review discusses updates in pathological T staging, adenocarcinoma grading and STAS and illustrates the utility and limitations of current concepts in lung adenocarcinoma.
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Affiliation(s)
- Jonathan Willner
- Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
| | - Navneet Narula
- Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
| | - Andre L Moreira
- Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
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20
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Wang S, Chen S, Li H, Ben S, Zhao T, Zheng R, Wang M, Gu D, Liu L. Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS. J Biomed Res 2023; 38:37-50. [PMID: 38111199 PMCID: PMC10818172 DOI: 10.7555/jbr.37.20230081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/26/2023] [Accepted: 05/28/2023] [Indexed: 12/20/2023] Open
Abstract
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis, but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking. To address this gap, we conducted a study aiming to investigate this association and identify relevant biomarkers. We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment, biological activity, and the immune microenvironment. Additionally, we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies (GWASs) involving both East Asian (7062 cases and 195745 controls) and European (24476 cases and 23073 controls) populations. We employed mediation analysis to infer the causal pathway, and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells. Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1 ( FEN1) gene were significantly enriched in colorectal tumor tissues, compared with normal tissues. Moreover, a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer (odds ratio = 0.94, 95% confidence interval: 0.90-0.97, P meta = 4.70 × 10 -9). Importantly, we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors, and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication. In conclusion, this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity, expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
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Affiliation(s)
- Sumeng Wang
- Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Silu Chen
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Huiqin Li
- Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Shuai Ben
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Tingyu Zhao
- Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Rui Zheng
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Meilin Wang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Dongying Gu
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
| | - Lingxiang Liu
- Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Ribatti D, Annese T, Tamma R. Vascular co-option in resistance to anti-angiogenic therapy. Front Oncol 2023; 13:1323350. [PMID: 38148844 PMCID: PMC10750409 DOI: 10.3389/fonc.2023.1323350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 11/23/2023] [Indexed: 12/28/2023] Open
Abstract
Three different mechanisms of neovascularization have been described in tumor growth, including sprouting angiogenesis, intussusceptive microvascular growth and glomeruloid vascular proliferation. Tumors can also grow by means of alternative mechanisms including vascular co-option, vasculogenic mimicry, angiotropism, and recruitment of endothelial precursor cells. Vascular co-option occurs in tumors independently of sprouting angiogenesis and the non-angiogenic cancer cells are described as exploiting pre-existing vessels. Vascular co-option is more frequently observed in tumors of densely vascularized organs, including the brain, lung and liver, and vascular co-option represents one of the main mechanisms involved in metastasis, as occurs in liver and lung, and resistance to anti-angiogenic therapy. The aim of this review article is to analyze the role of vascular co-option as mechanism through which tumors develop resistance to anti-angiogenic conventional therapeutic approaches and how blocking co-option can suppress tumor growth.
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Affiliation(s)
- Domenico Ribatti
- Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, Bari, Italy
| | - Tiziana Annese
- Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, Bari, Italy
- Department of Medicine and Surgery, Libera Università del Mediterraneo (LUM) Giuseppe Degennaro University, Bari, Italy
| | - Roberto Tamma
- Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, Bari, Italy
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22
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Wang J, Yao Y, Tang D, Gao W. An individualized nomogram for predicting and validating spread through air space (STAS) in surgically resected lung adenocarcinoma: a single center retrospective analysis. J Cardiothorac Surg 2023; 18:337. [PMID: 37990253 PMCID: PMC10664312 DOI: 10.1186/s13019-023-02458-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 11/15/2023] [Indexed: 11/23/2023] Open
Abstract
OBJECTIVE A single-center study was conducted to explore the association between STAS and other clinical features in surgically resected adenocarcinoma to enhance our current understanding of STAS. METHODS We retrospectively enrolled patients with lung adenocarcinoma (n = 241) who underwent curative surgeries. Patients undergoing surgery in 2019 were attributed to the training group (n = 188) and those undergoing surgery in January 2022 to June 2022 were attributed to the validation (n = 53) group. Univariate and multivariate logistic regression analyses were used to identify predictive factors for STAS, which were used to construct a simple nomogram. Furthermore, ROC and calibration curves were used to evaluate the performance of the nomogram. In addition, we conducted decision curve analysis (DCA) to assess the clinical utility of this nomogram. RESULTS In our cohort, 52 patients were identified as STAS-positive (21.6%). In univariate analysis, STAS was significantly associated with age, surgical approach, CEA, CTR (Consolidation Tumor Ratio), TNM stage, tumor grade, gross tumor size, resection margin, vessel cancer embolus, pleural invasion, lymph node metastasis, high ki67 and positive PD-L1 staining (P < 0.05). Lower age, CTR > 0.75, vessel cancer embolus, high Ki67 and PD-L1 stain positive were significant predictors for STAS during multivariate logistics analysis. A simple nomogram was successfully constructed based on these five predictors. The AUC values of our nomogram for the probability of tumor STAS were 0.860 in the training group and 0.919 in the validation group. In addition, the calibration curve and DCA validated the good performance of this model. CONCLUSION A nomogram was successfully constructed to identify the presence of STAS in surgically resected lung adenocarcinoma patients.
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Affiliation(s)
- Jing Wang
- Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200041, China
| | - Yuanshan Yao
- Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200041, China
| | - Dongfang Tang
- Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200041, China
| | - Wen Gao
- Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200041, China.
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23
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Dizbay Sak S, Sevim S, Buyuksungur A, Kayı Cangır A, Orhan K. The Value of Micro-CT in the Diagnosis of Lung Carcinoma: A Radio-Histopathological Perspective. Diagnostics (Basel) 2023; 13:3262. [PMID: 37892083 PMCID: PMC10606474 DOI: 10.3390/diagnostics13203262] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/12/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023] Open
Abstract
Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both quantitative and qualitative information on various types of samples. Micro-CT could potentially be used to examine human diseases and several studies have been published on this topic in the last decade. In this study, the potential uses of micro-CT in understanding and evaluating lung carcinoma and the relevant studies conducted on lung and other tumors are summarized. Currently, the resolution of benchtop laboratory micro-CT units has not reached the levels that can be obtained with light microscopy, and it is not possible to detect the histopathological features (e.g., tumor type, adenocarcinoma pattern, spread through air spaces) required for lung cancer management. However, its ability to provide 3D images in any plane of section, without disturbing the integrity of the specimen, suggests that it can be used as an auxiliary technique, especially in surgical margin examination, the evaluation of tumor invasion in the entire specimen, and calculation of primary and metastatic tumor volume. Along with future developments in micro-CT technology, it can be expected that the image resolution will gradually improve, the examination time will decrease, and the relevant software will be more user friendly. As a result of these developments, micro-CT may enter pathology laboratories as an auxiliary method in the pathological evaluation of lung tumors. However, the safety, performance, and cost effectiveness of micro-CT in the areas of possible clinical application should be investigated. If micro-CT passes all these tests, it may lead to the convergence of radiology and pathology applications performed independently in separate units today, and the birth of a new type of diagnostician who has equal knowledge of the histological and radiological features of tumors.
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Affiliation(s)
- Serpil Dizbay Sak
- Department of Pathology, Faculty of Medicine, Ankara University, Ankara 06230, Turkey
| | - Selim Sevim
- Department of Pathology, Faculty of Medicine, Ankara University, Ankara 06230, Turkey
| | - Arda Buyuksungur
- Department of Basic Medical Sciences, Faculty of Dentistry, Ankara University, Ankara 06560, Turkey
| | - Ayten Kayı Cangır
- Department of Thoracic Surgery Ankara, Faculty of Medicine, Ankara University, Ankara 06230, Turkey
| | - Kaan Orhan
- Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Ankara University, Ankara 06560, Turkey
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24
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Wang WJ, Chu LX, He LY, Zhang MJ, Dang KT, Gao C, Ge QY, Wang ZG, Zhao XW. Spatial transcriptomics: recent developments and insights in respiratory research. Mil Med Res 2023; 10:38. [PMID: 37592342 PMCID: PMC10433685 DOI: 10.1186/s40779-023-00471-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 07/24/2023] [Indexed: 08/19/2023] Open
Abstract
The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.
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Affiliation(s)
- Wen-Jia Wang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Liu-Xi Chu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
| | - Li-Yong He
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Ming-Jing Zhang
- Orthopaedic Bioengineering Research Group, Division of Surgery and Interventional Science, University College London, London, HA7 4LP, UK
| | - Kai-Tong Dang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Chen Gao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Qin-Yu Ge
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Zhou-Guang Wang
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
| | - Xiang-Wei Zhao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
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25
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Li Y, Byun AJ, Choe JK, Lu S, Restle D, Eguchi T, Tan KS, Saini J, Huang J, Rocco G, Jones DR, Travis WD, Adusumilli PS. Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma. J Thorac Oncol 2023; 18:608-619. [PMID: 36681298 PMCID: PMC10122702 DOI: 10.1016/j.jtho.2023.01.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/15/2022] [Accepted: 01/03/2023] [Indexed: 01/19/2023]
Abstract
INTRODUCTION High-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary (MIP), solid (SOL), or both patterns in lymph node (LN) metastases has prognostic value. METHODS Patients who underwent lobectomy for pathologic stages II to III lung ADC with N1 or N2 LN metastases (N = 360; 2000-2012) were analyzed. We assessed overall survival (OS), lung cancer-specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases. Multivariable Cox regression analysis was used to quantify the association between MIP/SOL patterns and outcomes. RESULTS MIP and SOL in LN metastases were associated with a higher incidence of smoking history (p = 0.004), tumor necrosis (p = 0.013), and spread of tumor through air spaces (p < 0.0001), a higher prevalence of MIP or SOL in the primary tumor (p < 0.0001), shorter OS (5-y OS, 40% [95% confidence interval or CI: 29%-56%] versus 63% [48%-83%] for no MIP/SOL in LNs, p = 0.03), higher LC-CID (5-y, 43% [29%-56%] versus 14% [4%-29%], p = 0.013), and higher CIR (5-y, 65% [50%-77%] versus 43% [25%-60%], p = 0.057). MIP and SOL in LN metastases were independently associated with poor outcomes: OS (hazard ratio [HR] = 1.81 [95% CI: 1.00-3.29], p = 0.05), LC-CID (HR = 3.10 [1.30-7.37], p = 0.01), and CIR (HR = 2.06 [1.09-3.90], p = 0.026). CONCLUSIONS MIP/SOL histologic patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stages II to III lung ADC. MIP/SOL histologic patterns in LN metastases can stratify patients with high-risk stages II to III lung ADC.
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Affiliation(s)
- Yan Li
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Hubei, People's Republic of China
| | - Alexander J Byun
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jennie K Choe
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Shaohua Lu
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - David Restle
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Takashi Eguchi
- Division of Thoracic Surgery, Department of Surgery, Shinshu University, Matsumoto, Japan
| | - Kay See Tan
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jasmeen Saini
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - James Huang
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Gaetano Rocco
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - David R Jones
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William D Travis
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Prasad S Adusumilli
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York.
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Li X, Zhang B, Liang Y, Li T. Multiscale reconstruction of bronchus and cancer cells in human lung adenocarcinoma. Biomed Eng Online 2023; 22:11. [PMID: 36755325 PMCID: PMC9906908 DOI: 10.1186/s12938-023-01072-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 01/25/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND While previous studies primarily focused on the structure of the normal whole mouse lung, the whole bronchus and cytoarchitectural details of the mouse intact lung lobe have been discovered at single-cell resolution. Revealing the sophisticated lung adenocarcinoma structure at three-dimensional (3D) and single-cell level remains a fundamental and critical challenge for the pathological mechanism research of lung adenocarcinoma (LA). METHODS Fluorescence micro-optical Sectioning Tomography (fMOST) combined with PI staining were used to obtain the 3D imaging of the human LA tissue at single-cell resolution. RESULTS With a spatial resolution of 0.32 × 0.32 × 1.0 μm3, the dataset of human LA with single-cell precision consists of two channels, each of which contains information about the bronchi and the cytoarchitecture. The bronchial wall is thicker and the lumen is smaller in the cancer tissue, in which its original normal structure is vanished. More solid components, more clustered cancer cells with larger nucleoli, and more significant atypia are found in cancer tissue. In paracancerous tissue, the bronchial wall cells have a monolayer or bilayer structure, cluster along the wall, and are relatively dispersed. Few fibrous structures and occasional dissemination of spread through air spaces (STAS) are observed. CONCLUSIONS Based on the human LA tissue dataset obtained by fMOST and PI staining, the bronchi and cells were reconstructed and visualized. This work provides a technical roadmap for studying the bronchus and cytoarchitectural structure and their spatial relationship in LA tissue, which may help with the understanding of the main histological structure of LA among pathologists.
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Affiliation(s)
- Xin Li
- grid.417020.00000 0004 6068 0239Department of Thoracic Surgery, Tianjin Chest Hospital (Affiliated Hospital of Tianjin University), Tianjin, China
| | - Bowen Zhang
- grid.506261.60000 0001 0706 7839Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, No.236 Baidi Road, Nankai District, Tianjin, 300192 China
| | - Yanmei Liang
- Institute of Modern Optics, Tianjin Key Laboratory of Micro-Scale Optical Information Science and Technology, Nankai University, Tianjin, China.
| | - Ting Li
- Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, No.236 Baidi Road, Nankai District, Tianjin, 300192, China.
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Yamada K, Kadota K, Fujimoto S, Yoshida C, Ibuki E, Ishikawa R, Haba R, Yokomise H, Yajima T. MMP-7 expression is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas. Lung Cancer 2023; 175:125-130. [PMID: 36508772 DOI: 10.1016/j.lungcan.2022.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The spread through air spaces (STAS) of adenocarcinoma (ADC) is a unique pattern for local invasion, which comprises the spread of tumor cells within air spaces beyond the tumor edge without a direct connection with the primary tumor. Matrix metalloproteinase-7 (MMP-7), a secreted proteolytic enzyme that degrades various extracellular matrix components and other substrates, regulates several pathophysiological processes as well as the occurrence and development of cancers in humans. Here, we retrospectively analyzed a cohort of Japanese patients with treatment-naive, surgically-resected lung ADC to assess whether MMP-7 is associated with STAS development and if it could be used as a predictor of STAS. MATERIALS AND METHODS We performed histological evaluation using hematoxylin and eosin staining and immunohistochemical analysis using microarrays. Thereafter, we scored the examined tissues for immune markers to identify significant tumor STAS predictors. RESULTS We identified that high MMP-7 expression is an independent predictor of a high STAS incidence. Multivariate analysis revealed that MMP-7 expression was correlated with tumor behavior and poor prognosis. Furthermore, STAS remained significantly associated with a higher risk of ADC recurrence. CONCLUSION The development of tumor STAS could be promoted by the functioning of MMP-7. This study could be a crucial basis for future investigations on the detection of tumor STAS.
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Affiliation(s)
- Kaede Yamada
- Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Kyuichi Kadota
- Department of Pathology, Faculty of Medicine, Shimane University, Shimane, Japan.
| | - Syusuke Fujimoto
- Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Chihiro Yoshida
- Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan; Department of General Thoracic Surgery, Kochi Health Sciences Center, Kochi, Japan
| | - Emi Ibuki
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Ryo Ishikawa
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Reiji Haba
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hiroyasu Yokomise
- Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Toshiki Yajima
- Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
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Pac J, Koo DJ, Cho H, Jung D, Choi MH, Choi Y, Kim B, Park JU, Kim SY, Lee Y. Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores. SCIENCE ADVANCES 2022; 8:eadd9419. [PMID: 36383671 PMCID: PMC9668299 DOI: 10.1126/sciadv.add9419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/29/2022] [Indexed: 06/16/2023]
Abstract
Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.
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Affiliation(s)
- Jinyoung Pac
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Dong-Jun Koo
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea
| | - Hyeongjun Cho
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea
| | - Dongwook Jung
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Min-ha Choi
- Department of Plastic and Reconstructive Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, 5 Gil 20, Boramae Road, Dongjak-Gu, Seoul 07061, South Korea
| | - Yunjung Choi
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Bohyun Kim
- Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Ji-Ung Park
- Department of Plastic and Reconstructive Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, 5 Gil 20, Boramae Road, Dongjak-Gu, Seoul 07061, South Korea
| | - Sung-Yon Kim
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea
| | - Yan Lee
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
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29
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A Nomogram Incorporating Tumor-Related Vessels for Differentiating Adenocarcinoma In Situ from Minimally Invasive and Invasive Adenocarcinoma Appearing as Subsolid Nodules. Acad Radiol 2022; 30:928-939. [PMID: 36150965 DOI: 10.1016/j.acra.2022.08.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 08/08/2022] [Accepted: 08/20/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To develop a nomogram incorporating the quantity of tumor-related vessels (TRVs) and conventional CT features (CCTFs) for the preoperative differentiation of adenocarcinoma in situ (AIS) from minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) appearing as subsolid nodules. METHODS High-resolution CT target scans of 274 subsolid nodules from 268 patients were included in this study and randomly assigned to the training and validation groups at a ratio of 7:3. A nomogram incorporating CCTFs with the category of TRVs (CTRVs, using TRVs as categorical variables) and a final nomogram combining the number of TRVs (QTRVs) and CCTFs were constructed using multivariable logistic regression analysis. The performance levels of the two nomograms were evaluated and validated on the training and validation datasets and then compared. RESULTS The CCTF-QTRV nomogram incorporating abnormal air bronchogram, density, number of dilated and distorted vessels and number of adherent vessels showed more favorable predictive efficacy than the CCTF-CTRV nomogram (training cohort: area under the curve (AUC) = 0.893 vs. 0.844, validation cohort: AUC = 0.871 vs. 0.807). The net reclassification index (training cohort: 0.188, validation cohort: 0.326) and the integrated discrimination improvement values (training cohort: 0.091, validation cohort: 0.125) indicated that the CCTF-QTRV nomogram performed significantly better discriminative ability than the CCTF-CTRV nomogram (all p-value < 0.05). CONCLUSIONS The nomogram incorporating the QTRVs and CCTFs showed favorable predictive efficacy for differentiating AIS from MIA-IAC appearing as subsolid nodules and may serve as a potential tool to provide individual care for these patients.
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Cuypers A, Truong ACK, Becker LM, Saavedra-García P, Carmeliet P. Tumor vessel co-option: The past & the future. Front Oncol 2022; 12:965277. [PMID: 36119528 PMCID: PMC9472251 DOI: 10.3389/fonc.2022.965277] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/04/2022] [Indexed: 12/11/2022] Open
Abstract
Tumor vessel co-option (VCO) is a non-angiogenic vascularization mechanism that is a possible cause of resistance to anti-angiogenic therapy (AAT). Multiple tumors are hypothesized to primarily rely on growth factor signaling-induced sprouting angiogenesis, which is often inhibited during AAT. During VCO however, tumors invade healthy tissues by hijacking pre-existing blood vessels of the host organ to secure their blood and nutrient supply. Although VCO has been described in the context of AAT resistance, the molecular mechanisms underlying this process and the profile and characteristics of co-opted vascular cell types (endothelial cells (ECs) and pericytes) remain poorly understood, resulting in the lack of therapeutic strategies to inhibit VCO (and to overcome AAT resistance). In the past few years, novel next-generation technologies (such as single-cell RNA sequencing) have emerged and revolutionized the way of analyzing and understanding cancer biology. While most studies utilizing single-cell RNA sequencing with focus on cancer vascularization have centered around ECs during sprouting angiogenesis, we propose that this and other novel technologies can be used in future investigations to shed light on tumor EC biology during VCO. In this review, we summarize the molecular mechanisms driving VCO known to date and introduce the models used to study this phenomenon to date. We highlight VCO studies that recently emerged using sequencing approaches and propose how these and other novel state-of-the-art methods can be used in the future to further explore ECs and other cell types in the VCO process and to identify potential vulnerabilities in tumors relying on VCO. A better understanding of VCO by using novel approaches could provide new answers to the many open questions, and thus pave the way to develop new strategies to control and target tumor vascularization.
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Affiliation(s)
- Anne Cuypers
- Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), Vlaams Instituut voor Biotechnologie (VIB) and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium
| | - Anh-Co Khanh Truong
- Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), Vlaams Instituut voor Biotechnologie (VIB) and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium
| | - Lisa M. Becker
- Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), Vlaams Instituut voor Biotechnologie (VIB) and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium
| | - Paula Saavedra-García
- Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Peter Carmeliet
- Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), Vlaams Instituut voor Biotechnologie (VIB) and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium
- Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
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31
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Ding Y, Li J, Li X, Xu M, Geng H, Sun D. Impact of preoperative biopsy on tumor spread through air spaces in stage I non-small cell lung cancer: a propensity score-matched study. BMC Pulm Med 2022; 22:293. [PMID: 35907818 PMCID: PMC9339177 DOI: 10.1186/s12890-022-02090-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 07/27/2022] [Indexed: 11/13/2022] Open
Abstract
Background Percutaneous needle biopsy (PNB) and bronchoscopic biopsy (BB) are widely used in the preoperative diagnosis of pulmonary nodules, but whether PNB or BB may cause tumor spread through air spaces (STAS) has not been reported. Methods 433 postoperative patients with pathological stage I non-small cell lung cancer (NSCLC) from January 2015 to December 2018 at our hospital were enrolled and divided into PNB group (n = 40), BB group (n = 48) and non-biopsy group (n = 345). The PNB and BB groups were matched using propensity score matched (PSM) separately from the non-biopsy group, after which the effects of PNB and BB on STAS, recurrence-free survival (RFS) and overall survival (OS) were assessed. Results After PSM for 9 confounding factors (gender, age, smoking history, tumor site, scope of surgery, pathology type, stage, maximum tumor diameter and postoperative treatment), 38 cases in the PNB group were successfully matched with 38 cases in the non-biopsy group and 28 cases in the BB group were successfully matched with 28 cases in the non-biopsy group. After PSM, there was no significant difference in the incidence of STAS between the PNB and non-biopsy groups (42.1% vs. 34.2%, P > 0.05) and between the BB and non-biopsy groups (42.9% vs. 46.4%, P > 0.05). The results after PSM showed no significant effect of both PNB and BB on RFS and OS after radical surgery (P > 0.05). Conclusion Preoperative biopsy in patients with stage I NSCLC has not been shown to increase the occurrence of STAS, nor postoperative recurrence and death.
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Affiliation(s)
- Yun Ding
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, China
| | - Jiuzhen Li
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, China
| | - Xin Li
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, China.,Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China
| | - Meilin Xu
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, China.,Department of Pathology, Tianjin Chest Hospital, Tianjin, China
| | - Hua Geng
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, China.,Department of Pathology, Tianjin Chest Hospital, Tianjin, China
| | - Daqiang Sun
- Clinical School of Thoracic, Tianjin Medical University, Tianjin, China. .,Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China.
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32
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van Ineveld RL, van Vliet EJ, Wehrens EJ, Alieva M, Rios AC. 3D imaging for driving cancer discovery. EMBO J 2022; 41:e109675. [PMID: 35403737 PMCID: PMC9108604 DOI: 10.15252/embj.2021109675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 03/09/2022] [Accepted: 03/09/2022] [Indexed: 11/09/2022] Open
Abstract
Our understanding of the cellular composition and architecture of cancer has primarily advanced using 2D models and thin slice samples. This has granted spatial information on fundamental cancer biology and treatment response. However, tissues contain a variety of interconnected cells with different functional states and shapes, and this complex organization is impossible to capture in a single plane. Furthermore, tumours have been shown to be highly heterogenous, requiring large-scale spatial analysis to reliably profile their cellular and structural composition. Volumetric imaging permits the visualization of intact biological samples, thereby revealing the spatio-phenotypic and dynamic traits of cancer. This review focuses on new insights into cancer biology uniquely brought to light by 3D imaging and concomitant progress in cancer modelling and quantitative analysis. 3D imaging has the potential to generate broad knowledge advance from major mechanisms of tumour progression to new strategies for cancer treatment and patient diagnosis. We discuss the expected future contributions of the newest imaging trends towards these goals and the challenges faced for reaching their full application in cancer research.
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Affiliation(s)
- Ravian L van Ineveld
- Princess Máxima Center for Pediatric OncologyUtrechtThe Netherlands
- Oncode InstituteUtrechtThe Netherlands
| | - Esmée J van Vliet
- Princess Máxima Center for Pediatric OncologyUtrechtThe Netherlands
- Oncode InstituteUtrechtThe Netherlands
| | - Ellen J Wehrens
- Princess Máxima Center for Pediatric OncologyUtrechtThe Netherlands
- Oncode InstituteUtrechtThe Netherlands
| | - Maria Alieva
- Princess Máxima Center for Pediatric OncologyUtrechtThe Netherlands
- Oncode InstituteUtrechtThe Netherlands
| | - Anne C Rios
- Princess Máxima Center for Pediatric OncologyUtrechtThe Netherlands
- Oncode InstituteUtrechtThe Netherlands
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Tumour Cell Budding and Spread Through Air Spaces in Squamous Cell Carcinoma of the Lung – Determination and Validation of optimal prognostic cut-offs. Lung Cancer 2022; 169:1-12. [DOI: 10.1016/j.lungcan.2022.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 03/22/2022] [Accepted: 04/25/2022] [Indexed: 11/22/2022]
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Kramer CJH, Vreeswijk MPG, Thijssen B, Bosse T, Wesseling J. Beyond the snapshot: optimizing prognostication and prediction by moving from fixed to functional multidimensional cancer pathology. J Pathol 2022; 257:403-412. [PMID: 35438188 PMCID: PMC9324156 DOI: 10.1002/path.5915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/11/2022] [Accepted: 04/13/2022] [Indexed: 11/10/2022]
Abstract
The role of pathology in patient management has evolved over time from the retrospective review of cells, tissue, and disease (‘what happened’) to a prospective outlook (‘what will happen’). Examination of a static, two‐dimensional hematoxylin and eosin (H&E)‐stained tissue slide has traditionally been the pathologist's primary task, but novel ancillary techniques enabled by technological breakthroughs have supported pathologists in their increasing ability to predict disease status and behaviour. Nevertheless, the informational limits of 2D, fixed tissue are now being reached and technological innovation is urgently needed to ensure that our understanding of disease entities continues to support improved individualized treatment options. Here we review pioneering work currently underway in the field of cancer pathology that has the potential to capture information beyond the current basic snapshot. A selection of exciting new technologies is discussed that promise to facilitate integration of the functional and multidimensional (space and time) information needed to optimize the prognostic and predictive value of cancer pathology. Learning how to analyse, interpret, and apply the wealth of data acquired by these new approaches will challenge the knowledge and skills of the pathology community. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- C J H Kramer
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - M P G Vreeswijk
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
| | - B Thijssen
- Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands.,Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - T Bosse
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - J Wesseling
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.,Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.,Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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Yoshida M, Cesmecioglu E, Firat C, Sakamoto H, Teplov A, Kawata N, Ntiamoah P, Ohnishi T, Ibrahim K, Vakiani E, Garcia-Aguilar J, Hameed M, Shia J, Yagi Y. Pathological Evaluation of Rectal Cancer Specimens Using Micro-Computed Tomography. Diagnostics (Basel) 2022; 12:diagnostics12040984. [PMID: 35454033 PMCID: PMC9044748 DOI: 10.3390/diagnostics12040984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 04/12/2022] [Indexed: 12/10/2022] Open
Abstract
Whole-block imaging (WBI) using micro-computed tomography (micro-CT) allows the nondestructive reconstruction of a three-dimensional view of tissues, implying that WBI may be used for accurate pathological evaluation of patients with rectal cancer. HOWEVER, the clinical impact of this approach is unclear. We aimed to clarify the efficacy of WBI in the whole-mount specimens of locally advanced rectal cancer. A total of 237 whole-mount formalin-fixed paraffin-embedded blocks from 13 patients with rectal cancer who underwent surgical treatment were enrolled and scanned with micro-CT to generate three-dimensional images. WBI was evaluated following the conventional pathological review of the corresponding whole-slide imaging (WSI). WBI identified all tumor sites detected using WSI. Furthermore, WBI revealed one additional tumor site, which was not detected using WSI. Tumor resection margin was significantly closer to the soft-tissue edge when measured using WBI (7.7 mm vs. 6.6 mm, p < 0.01). Seventy-six percent of tumor deposits on WSI were changed according to the evidence of tumor interaction with the surrounding tissues confirmed using WBI. Furthermore, WBI revealed 25 additional lymph nodes, six of which were metastatic. The combination of conventional hematoxylin and eosin-stained imaging and WBI may contribute to an accurate pathological assessment.
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Affiliation(s)
- Masao Yoshida
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan;
- Correspondence: ; Tel.: +1-646-888-7617; Fax: +1-929-321-7025
| | - Emine Cesmecioglu
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
- Department of Pathology, Marmara University Research and Education Hospital, Istanbul 34899, Turkey
| | - Canan Firat
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Hirotsugu Sakamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi 329-0498, Japan;
| | - Alexei Teplov
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan;
| | - Peter Ntiamoah
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Takashi Ohnishi
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Kareem Ibrahim
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;
| | - Meera Hameed
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
| | - Yukako Yagi
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.); (C.F.); (A.T.); (P.N.); (T.O.); (K.I.); (E.V.); (M.H.); (J.S.); (Y.Y.)
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Chae M, Cho S, Chung JH, Yum S, Kim K, Jheon S. Poor Prognosis of Grade 2 Spread Through Air Spaces in Neuroendocrine Tumors. J Chest Surg 2022; 55:101-107. [PMID: 35232897 PMCID: PMC9005938 DOI: 10.5090/jcs.21.097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 12/08/2021] [Accepted: 12/29/2021] [Indexed: 11/16/2022] Open
Abstract
Background Spread through air spaces (STAS) has recently emerged as a prognostic factor in lung adenocarcinoma, but little is known about the association of STAS and its grade with recurrence in neuroendocrine tumors (NETs). This study investigated the prognostic effect of STAS grade in NETs after curative resection. Methods Seventy-seven patients were retrospectively reviewed, including 9 with typical carcinoid (TC), 6 with atypical carcinoid (AC), 26 with large cell neuroendocrine carcinoma (LCNEC), and 36 with small cell carcinoma (SCC). STAS was defined as the presence of floating tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. STAS was classified as grade 1 or 2 depending on whether it was found within or beyond one ×10 objective lens field away from the main tumor margin, respectively. Results Fifty-four patients (70%) had STAS, including 22% with TC, 50% with AC, 69% with LCNEC, and 86% with SCC. Patients with STAS had more nodal metastasis, lymphatic and vascular invasion, tumor necrosis, and tumor subtypes other than TC. Among STAS cases, grade 2 STAS was present in 33% of AC, 78% of LCNEC, and 87% of SCC. The 5-year recurrence-free survival (RFS) rate was 81%, 63%, and 35% in patients with no STAS, grade 1, and grade 2 STAS, respectively. Multivariate analysis found that grade 2 STAS was an independent negative prognostic factor for RFS. Conclusion Although STAS itself was not associated with a poor prognosis, grade 2 STAS was an independent negative prognostic factor for RFS.
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Affiliation(s)
- Mincheol Chae
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sukki Cho
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Haeng Chung
- Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Sungwon Yum
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kwhanmien Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sanghoon Jheon
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea
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37
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Choueiri TK, Albiges L, Atkins MB, Bakouny Z, Bratslavsky G, Braun DA, Haas NB, Haanen JB, Hakimi AA, Jewett MA, Jonasch E, Kaelin WG, Kapur P, Labaki C, Lewis B, McDermott DF, Pal SK, Pels K, Poteat S, Powles T, Rathmell WK, Rini BI, Signoretti S, Tannir NM, Uzzo RG, Hammers HJ. From Basic Science to Clinical Translation in Kidney Cancer: A Report from the Second Kidney Cancer Research Summit. Clin Cancer Res 2022; 28:831-839. [PMID: 34965942 PMCID: PMC9223120 DOI: 10.1158/1078-0432.ccr-21-3238] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/07/2021] [Accepted: 12/21/2021] [Indexed: 11/16/2022]
Abstract
The second Kidney Cancer Research Summit was held virtually in October 2020. The meeting gathered worldwide experts in the field of kidney cancer, including basic, translational, and clinical scientists as well as patient advocates. Novel studies were presented, addressing areas of unmet need related to different topics. These include novel metabolic targets, promising immunotherapeutic regimens, predictive genomic and transcriptomic biomarkers, and variant histologies of renal cell carcinoma (RCC). With the development of pioneering technologies, and an unprecedented commitment to kidney cancer research, the field has tremendously evolved. This perspective aims to summarize the different sessions of the conference, outline major advances in the understanding of RCC and discuss current challenges faced by the field.
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Affiliation(s)
- Toni K. Choueiri
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Laurence Albiges
- Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Michael B. Atkins
- Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA
| | - Ziad Bakouny
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Gennady Bratslavsky
- Department of Urology, State University of New York (SUNY) Upstate Medical University, Syracuse, New York
| | - David A. Braun
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Naomi B. Haas
- Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - John B.A.G. Haanen
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - A Ari Hakimi
- Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael A.S. Jewett
- Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Eric Jonasch
- Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - William G. Kaelin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Payal Kapur
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Chris Labaki
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | | | - David F. McDermott
- Division of Medical Oncology, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts
| | - Sumanta K. Pal
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Kevin Pels
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | | | - Thomas Powles
- Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - W. Kimryn Rathmell
- Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, TN, USA
| | - Brian I. Rini
- Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, TN, USA
| | - Sabina Signoretti
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Nizar M. Tannir
- Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Robert G. Uzzo
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Hans J. Hammers
- Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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38
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Corcione N, Ponticiello A, Campione S, Pecoraro A, Moccia L, Failla G. A case of haemoptysis and bilateral areas of lung consolidation sparing the right lower lobe. Breathe (Sheff) 2022; 17:210072. [PMID: 35035564 PMCID: PMC8753663 DOI: 10.1183/20734735.0072-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 09/07/2021] [Indexed: 11/23/2022] Open
Abstract
Multiple primary lung cancers (MPLC) are often neglected. Obtaining pre-operative specimens through bronchoscopy could play a role. It is important to distinguish aerogenous metastasis from MPLC in the adenocarcinoma spectrum due to the different prognosis.https://bit.ly/3zbdVrw
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Affiliation(s)
- Nadia Corcione
- Interventional Pulmonology Unit, Dept of Pulmonology, Oncology and Hematology, Cardarelli Hospital, Naples, Italy
| | - Antonio Ponticiello
- University of Naples Federico II, School of Medicine and Surgery, Naples, Italy
| | - Severo Campione
- Pathology Unit, Dept of Advanced Technology, Cardarelli Hospital, Naples, Italy
| | - Alfonso Pecoraro
- Interventional Pulmonology Unit, Dept of Pulmonology, Oncology and Hematology, Cardarelli Hospital, Naples, Italy
| | - Livio Moccia
- Interventional Pulmonology Unit, Dept of Pulmonology, Oncology and Hematology, Cardarelli Hospital, Naples, Italy
| | - Giuseppe Failla
- Interventional Pulmonology Unit, Dept of Pulmonology, Oncology and Hematology, Cardarelli Hospital, Naples, Italy
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He YF, Chen JW, An CZ, Hou XL, Zhong ZT, Li CQ, Chen W, Liu B, Zhao YD. Labeling of liver cells with CdSe/ZnS quantum dot-based fluorescence probe below freezing point. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2021; 263:120203. [PMID: 34325172 DOI: 10.1016/j.saa.2021.120203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/22/2021] [Accepted: 07/15/2021] [Indexed: 06/13/2023]
Abstract
In this paper, CdSe/ZnS quantum dots (QDs) with particle size of 5.5 ~ 9.3 nm were synthesized, and the fluorescence emission ranged from 545 ~ 616 nm. When the volume fraction of ethanol was 30%, the water-soluble QD dispersion system remained liquid under -20 °C freezing conditions, the fluorescence intensity increased with a decrease in temperature, and the quantum yield reached 79% at -20 °C. The endothelial cell adhesion molecule CD31 antibody (anti-CD31) was used as the primary antibody, QDs were coupled with IgG as the secondary antibody (QD-Ab), and effective labeling of hepatic sinusoid endothelial cells was achieved at -20 °C. Fluorescence imaging and flow cytometry analysis showed that the labeling efficiency was as high as 97%, indicating that QDs have an important application prospect in microscopic section tomography of the liver.
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Affiliation(s)
- Yan-Fei He
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Jian-Wei Chen
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Chang-Zhi An
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Xiao-Lin Hou
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Zi-Tao Zhong
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Chao-Qing Li
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Wei Chen
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Bo Liu
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China
| | - Yuan-Di Zhao
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China; Key Laboratory of Biomedical Photonics (HUST), Ministry of Education, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
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40
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Cao L, Tong Y, Wang X, Zhang Q, Qi Y, Zhou C, Yu X, Wu Y, Miao X. Effect of Amniotic Membrane/Collagen-Based Scaffolds on the Chondrogenic Differentiation of Adipose-Derived Stem Cells and Cartilage Repair. Front Cell Dev Biol 2021; 9:647166. [PMID: 34900977 PMCID: PMC8657407 DOI: 10.3389/fcell.2021.647166] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 10/20/2021] [Indexed: 11/24/2022] Open
Abstract
Objectives: Repairing articular cartilage damage is challenging. Clinically, tissue engineering technology is used to induce stem cell differentiation and proliferation on biological scaffolds to repair defective joints. However, no ideal biological scaffolds have been identified. This study investigated the effects of amniotic membrane/collagen scaffolds on the differentiation of adipose-derived stem cells (ADSCs) and articular cartilage repair. Methods: Adipose tissue of New Zealand rabbits was excised, and ADSCs were isolated and induced for differentiation. An articular cartilage defect model was constructed to identify the effect of amniotic membrane/collagen scaffolds on cartilage repair. Cartilage formation was analyzed by imaging and toluene blue staining. Knee joint recovery in rabbits was examined using hematoxylin and eosin, toluidine, safranine, and immunohistochemistry at 12 weeks post-operation. Gene expression was examined using ELISA, RT-PCR, Western blotting, and immunofluorescence. Results: The adipose tissue was effectively differentiated into ADSCs, which further differentiated into chondrogenic, osteogenic, and lipogenic lineages after 3 weeks’ culture in vitro. Compared with platelet-rich plasmon (PRP) scaffolds, the amniotic membrane scaffolds better promoted the growth and differentiation of ADSCs. Additionally, scaffolds containing the PRP and amniotic membrane efficiently enhanced the osteogenic differentiation of ADSCs. The levels of COL1A1, COL2A1, COL10A1, SOX9, and ACAN in ADSCs + amniotic membrane + PRP group were significantly higher than the other groups both in vitro and in vivo. The Wakitani scores of the ADSC + amniotic membrane + PRP group were lower than that in ADSC + PRP (4.4 ± 0.44**), ADSC + amniotic membrane (2.63 ± 0.38**), and control groups (6.733 ± 0.21) at week 12 post-operation. Osteogenesis in rabbits of the ADSC + amniotic membrane + PRP group was significantly upregulated when compared with other groups. Amniotic membranes significantly promoted the expression of cartilage regeneration-related factors (SOX6, SOX9, RUNX2, NKX3-2, MEF2C, and GATA4). The ADSC + PRP + amniotic membrane group exhibited the highest levels of TGF-β, PDGF, and FGF while exhibiting the lowest level of IL-1β, IL6, and TNF-α in articular cavity. Conclusion: Amniotic membrane/collagen combination-based scaffolds promoted the proliferation and cartilage differentiation of ADSCs, and may provide a new treatment paradigm for patients with cartilage injury.
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Affiliation(s)
- Le Cao
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Yuling Tong
- Department of General Practice, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao Wang
- Shaoxing Shangyu Hospital of Traditional Chinese medicine, Shaoxing, China
| | - Qiang Zhang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Yiying Qi
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Chenhe Zhou
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Xinning Yu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Yongping Wu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Xudong Miao
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
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41
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Lamort AS, Kaiser JC, Pepe MAA, Lilis I, Ntaliarda G, Somogyi K, Spella M, Behrend SJ, Giotopoulou GA, Kujawa W, Lindner M, Koch I, Hatz RA, Behr J, Sotillo R, Schamberger AC, Stathopoulos GT. Prognostic phenotypes of early-stage lung adenocarcinoma. Eur Respir J 2021; 60:13993003.01674-2021. [PMID: 34887322 DOI: 10.1183/13993003.01674-2021] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 11/11/2021] [Indexed: 11/05/2022]
Abstract
BACKGROUND Survival after curative resection of early-stage lung adenocarcinoma (LUAD) varies and prognostic biomarkers are urgently needed. METHODS Large-format tissue samples from a prospective cohort of 200 patients with resected LUAD were immunophenotyped for cancer hallmarks TP53, NF1, CD45, PD-1, PCNA, TUNEL, and FVIII, and were followed for median (95%CI)=2.34 (1.71-3.49) years. RESULTS Unsupervised hierarchical clustering revealed two patient subgroups with similar clinicopathologic features and genotype, but with markedly different survival: "proliferative" patients (60%) with elevated TP53, NF1, CD45, and PCNA expression had 50% 5-year overall survival while "apoptotic" patients (40%) with high TUNEL had 70% 5-year survival [HR95%CI=2.23 (1.33-3.80); p=0.0069]. Cox regression and machine learning algorithms including random forests built clinically useful models: a score to predict overall survival and a formula and nomogram to predict tumour phenotype. The distinct LUAD phenotypes were validated in TCGA and KMplotter data and showed prognostic power supplementary to IASLC TNM stage and WHO histologic classification. CONCLUSIONS Two molecular subtypes of LUAD exist and their identification provides important prognostic information.
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Affiliation(s)
- Anne-Sophie Lamort
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany.,German Center for Lung Research, Gießen, Hesse, Germany.,Equally contributing authors
| | - Jan Christian Kaiser
- Institute of Radiation Medicine (IRM), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Neuherberg, Bavaria, Germany.,Equally contributing authors
| | - Mario A A Pepe
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany.,German Center for Lung Research, Gießen, Hesse, Germany
| | - Ioannis Lilis
- Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece
| | - Giannoula Ntaliarda
- Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece
| | - Kalman Somogyi
- German Center for Lung Research, Gießen, Hesse, Germany.,Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Magda Spella
- Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece
| | - Sabine J Behrend
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany.,German Center for Lung Research, Gießen, Hesse, Germany
| | - Georgia A Giotopoulou
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany.,German Center for Lung Research, Gießen, Hesse, Germany
| | - Willem Kujawa
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany.,German Center for Lung Research, Gießen, Hesse, Germany
| | - Michael Lindner
- German Center for Lung Research, Gießen, Hesse, Germany.,Center for Thoracic Surgery Munich, Ludwig-Maximilian-University of Munich and Asklepios Medical Center, Gauting, Bavaria, Germany
| | - Ina Koch
- German Center for Lung Research, Gießen, Hesse, Germany.,Center for Thoracic Surgery Munich, Ludwig-Maximilian-University of Munich and Asklepios Medical Center, Gauting, Bavaria, Germany
| | - Rudolf A Hatz
- German Center for Lung Research, Gießen, Hesse, Germany.,Center for Thoracic Surgery Munich, Ludwig-Maximilian-University of Munich and Asklepios Medical Center, Gauting, Bavaria, Germany
| | - Juergen Behr
- German Center for Lung Research, Gießen, Hesse, Germany.,Department of Medicine V, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Bavaria, Germany
| | - Rocio Sotillo
- German Center for Lung Research, Gießen, Hesse, Germany.,Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Translational Lung Research Center Heidelberg (TRLC), German Center for Lung Research (DZL), Heidelberg, Germany
| | - Andrea C Schamberger
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany.,German Center for Lung Research, Gießen, Hesse, Germany
| | - Georgios T Stathopoulos
- Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Bavaria, Germany .,German Center for Lung Research, Gießen, Hesse, Germany.,Equally contributing authors
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42
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Gross DJ, Hsieh MS, Li Y, Dux J, Rekhtman N, Jones DR, Travis WD, Adusumilli PS. Spread Through Air Spaces (STAS) in Non-Small Cell Lung Carcinoma: Evidence Supportive of an In Vivo Phenomenon. Am J Surg Pathol 2021; 45:1509-1515. [PMID: 34366424 PMCID: PMC8516688 DOI: 10.1097/pas.0000000000001788] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non-small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR.
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Affiliation(s)
- Daniel J. Gross
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Min-Shu Hsieh
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yan Li
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Pathology, Union Hospital, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Joseph Dux
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Natasha Rekhtman
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David R. Jones
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William D. Travis
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Prasad S. Adusumilli
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Haddad TS, Friedl P, Farahani N, Treanor D, Zlobec I, Nagtegaal I. Tutorial: methods for three-dimensional visualization of archival tissue material. Nat Protoc 2021; 16:4945-4962. [PMID: 34716449 DOI: 10.1038/s41596-021-00611-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 08/05/2021] [Indexed: 02/08/2023]
Abstract
Analysis of three-dimensional patient specimens is gaining increasing relevance for understanding the principles of tissue structure as well as the biology and mechanisms underlying disease. New technologies are improving our ability to visualize large volume of tissues with subcellular resolution. One resource often overlooked is archival tissue maintained for decades in hospitals and research archives around the world. Accessing the wealth of information stored within these samples requires the use of appropriate methods. This tutorial introduces the range of sample preparation and microscopy approaches available for three-dimensional visualization of archival tissue. We summarize key aspects of the relevant techniques and common issues encountered when using archival tissue, including registration and antibody penetration. We also discuss analysis pipelines required to process, visualize and analyze the data and criteria to guide decision-making. The methods outlined in this tutorial provide an important and sustainable avenue for validating three-dimensional tissue organization and mechanisms of disease.
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Affiliation(s)
- Tariq Sami Haddad
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
| | - Peter Friedl
- Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
- David H. Koch Center for Applied Research of Genitourinary Cancers, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Cancer GenomiCs.nl (CGC.nl), http://cancergenomics.nl, Utrecht, the Netherlands
| | | | - Darren Treanor
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
- Department of Clinical Pathology, and Department of Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden
- Center for Medical Imaging Science and Visualization (CMIV), Linköping, Sweden
| | - Inti Zlobec
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Iris Nagtegaal
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
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Peng B, Li G, Guo Y. Prognostic significance of micropapillary and solid patterns in stage IA lung adenocarcinoma. Am J Transl Res 2021; 13:10562-10569. [PMID: 34650727 PMCID: PMC8507014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 04/12/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE To evaluate the value of the non-predominant micropapillary and solid patterns in prognosis of lung adenocarcinoma. METHODS Totally 422 patients diagnosed with stage IA lung adenocarcinomas were included, and all their slides were reviewed. We compared clinicopathological characteristics and survival outcomes between MP- & SD- (both micropapillary and solid component were absent), MP+/SD+ (either micropapillary or solid component was present, but the single or combined percentage of the MP and SD was not greater than 50%) and MPp/SDp (either micropapillary or solid or the combined percentage of these two components was great than 50%). RESULTS Patients with MP- & SD- had smaller tumor size (P=0.012) and lower spread through air spaces rates (P<0.001). Patients with MP- & SD- had significantly better 5-year recurrence free survival than MP+/SD+ (91% versus 70%, P<0.001) and MPp/SDp (91% versus 56%, P<0.001). The difference of RFS between MP+/SD+ subgroup and MPp/SDp subgroup was not significant (P=0.177). In the multivariate analysis, patients with MP- & SD- had a better recurrence free survival than the other two groups (versus: MP+/SD+, HR, 3.198; 95% CI, 1.537-6.653; P=0.002; versus MPp/SDp: HR, 4.981; 95% CI, 2.266-10.950; P<0.001). CONCLUSIONS The presence of micropapillary or solid patterns, even not predominant, was a risk factor for predicting poor recurrence free survival in very early stage lung adenocarcinoma.
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Affiliation(s)
- Bin Peng
- Department of Thoracic Surgery, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan UniversityLuohu District, Shenzhen 518020, P. R. China
| | - Guofeng Li
- Department of Thoracic Surgery, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan UniversityLuohu District, Shenzhen 518020, P. R. China
| | - Yanhua Guo
- Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary HospitalShanghai 200433, P. R. China
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Yi E, Lee JH, Jung Y, Chung JH, Lee Y, Lee S. Clinical implication of tumour spread through air spaces in pathological stage I lung adenocarcinoma treated with lobectomy. Interact Cardiovasc Thorac Surg 2021; 32:64-72. [PMID: 33232453 DOI: 10.1093/icvts/ivaa227] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/21/2020] [Accepted: 09/03/2020] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVES The aim of this study was to evaluate the clinical implication of tumour spread through air spaces (STAS) as a prognostic factor in pathological stage I lung adenocarcinoma treated with lobectomy and to identify related parameters. METHODS Medical records of patients who underwent pulmonary lobectomy for stage I (American Joint Committee on Cancers eighth edition) lung adenocarcinomas between 2012 and February 2018 at our institutions were reviewed retrospectively. Patients with minimally invasive adenocarcinomas and tumours ≥3 cm in size were excluded. Included patients were classified into STAS (+) and STAS (-) groups. Clinical implications of STAS and recurrence in patients were investigated. RESULTS A total of 109 patients was analysed: 41 (37.6%) in the STAS (+) and 68 (62.4%) in the STAS (-) group. STAS was associated with larger consolidation diameter on chest tomography (≥1.5 cm; P = 0.006) or a higher invasive ratio (≥85%; P = 0.012) and presence of a micropapillary pattern in multivariable analysis (P = 0.003) The recurrence-free survival curve showed statistical difference (P = 0.008) with 3-year survival rates of 73.0% (9 patients) and 96.8% (2 patients) in the STAS (+) and STAS (-) group, respectively. However, no statistical significance was observed in the lung cancer-related survival curve (P = 0.648). The presence of STAS was an independent risk factor for recurrence in multivariable analysis (hazard ratio = 5.9, P = 0.031). CONCLUSIONS The presence of STAS could be an important risk factor for recurrence in patients with early-stage invasive lung adenocarcinoma treated with pulmonary lobectomy.
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Affiliation(s)
- Eunjue Yi
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul, Korea
| | - Jeong Hyeon Lee
- Department of Pathology, Korea University Anam Hospital, Seoul, Korea
| | - Younggi Jung
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul, Korea
| | - Jae Ho Chung
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul, Korea
| | - Youngseok Lee
- Department of Pathology, Korea University Anam Hospital, Seoul, Korea
| | - Sungho Lee
- Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Seoul, Korea
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Ikeda T, Kadota K, Go T, Haba R, Yokomise H. Current status and perspectives of spread through air spaces in lung cancer. Thorac Cancer 2021; 12:1639-1646. [PMID: 33951312 PMCID: PMC8169306 DOI: 10.1111/1759-7714.13918] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/16/2021] [Accepted: 02/16/2021] [Indexed: 12/17/2022] Open
Abstract
According to the World Health Organization classification of 2015, spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. Many researchers have reported that STAS is recognized in all histological subtypes, and there is a strong association between STAS and prognosis in lung cancer. However, there are several technical issues associated with STAS, such as distinction between the actual in vivo phenomenon and an artifact, difficulty in assessing STAS in frozen specimens, and establishing the relationship between morphological and molecular properties of STAS. This review focuses on the current state of knowledge and the outlook of the STAS phenomenon from the perspective of surgeons, pathologists, and radiologists.
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Affiliation(s)
- Toshihiro Ikeda
- Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Kyuichi Kadota
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Tetsuhiko Go
- Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Reiji Haba
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Hiroyasu Yokomise
- Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
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Deng X, Liu Y, Chen H. Three-dimensional image reconstruction based on improved U-net network for anatomy of pulmonary segmentectomy. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2021; 18:3313-3322. [PMID: 34198387 DOI: 10.3934/mbe.2021165] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Pulmonary segmentectomy is one of the advanced techniques in thoracic surgery, but it is difficult to understand and master because of its complex anatomical structure. The purpose of this study is to explore the application effect of three-dimensional (3D) image reconstruction based on an improved U-net network in the anatomy of thoracic surgery. In this study, a total of 40 standardization training residents of thoracic surgery in our hospital were randomly divided into two groups. The control group was taught by conventional thin-slice CT images, while the observation group was taught by 3D image reconstruction based on the improved U-net network. After the training process was completed, the teaching effect was compared between these two groups. Using the improved U-net network model, 3D reconstruction of pulmonary segments can be realized quickly. Compared with the control group, the individual and total objective scores in the observation group were higher. The satisfaction of learning interest, content understanding, clinical thinking mode, and understanding of operation process in the observation group was higher than that of the control group. From the results, we concluded that the 3D image reconstruction technology based on the improved U-net network could help students master the anatomical structure of pulmonary segments and improve their learning interest and clinical thinking ability.
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Affiliation(s)
- Xuefei Deng
- Department of Human Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Yu Liu
- Department of Human Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Hao Chen
- Department of Thoracic Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
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Haas G, Fan S, Ghadimi M, De Oliveira T, Conradi LC. Different Forms of Tumor Vascularization and Their Clinical Implications Focusing on Vessel Co-option in Colorectal Cancer Liver Metastases. Front Cell Dev Biol 2021; 9:612774. [PMID: 33912554 PMCID: PMC8072376 DOI: 10.3389/fcell.2021.612774] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 03/15/2021] [Indexed: 12/11/2022] Open
Abstract
In modern anti-cancer therapy of metastatic colorectal cancer (mCRC) the anti-angiogenic treatment targeting sprouting angiogenesis is firmly established for more than a decade. However, its clinical benefits still remain limited. As liver metastases (LM) represent the most common metastatic site of colorectal cancer and affect approximately one-quarter of the patients diagnosed with this malignancy, its treatment is an essential aspect for patients' prognosis. Especially in the perioperative setting, the application of anti-angiogenic drugs represents a therapeutic option that may be used in case of high-risk or borderline resectable colorectal cancer liver metastases (CRCLM) in order to achieve secondary resectability. Regarding CRCLM, one reason for the limitations of anti-angiogenic treatment may be represented by vessel co-option (VCO), which is an alternative mechanism of blood supply that differs fundamentally from the well-known sprouting angiogenesis and occurs in a significant fraction of CRCLM. In this scenario, tumor cells hijack pre-existing mature vessels of the host organ independently from stimulating new vessels formation. This represents an escape mechanism from common anti-angiogenic anti-cancer treatments, as they primarily target the main trigger of sprouting angiogenesis, the vascular endothelial growth factor A. Moreover, the mechanism of blood supply in CRCLM can be deduced from their phenotypic histopathological growth pattern (HGP). For that, a specific guideline has already been implemented. These HGP vary not only regarding their blood supply, but also concerning their tumor microenvironment (TME), as notable differences in immune cell infiltration and desmoplastic reaction surrounding the CRCLM can be observed. The latter actually serves as one of the central criteria for the classification of the HGP. Regarding the clinically relevant effects of the HGP, it is still a topic of research whether the VCO-subgroup of CRCLM results in an impaired treatment response to anti-angiogenic treatment when compared to an angiogenic subgroup. However, it is well-proved, that VCO in CRCLM generally relates to an inferior survival compared to the angiogenic subgroup. Altogether the different types of blood supply result in a relevant influence on the patients' prognosis. This reinforces the need of an extended understanding of the underlying mechanisms of VCO in CRCLM with the aim to generate more comprehensive approaches which can target tumor vessels alternatively or even other components of the TME. This review aims to augment the current state of knowledge on VCO in CRCLM and other tumor entities and its impact on anti-angiogenic anti-cancer therapy.
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Affiliation(s)
- Gwendolyn Haas
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany
| | - Shuang Fan
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany
| | - Michael Ghadimi
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany
| | - Tiago De Oliveira
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany
| | - Lena-Christin Conradi
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany
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Massagué J, Ganesh K. Metastasis-Initiating Cells and Ecosystems. Cancer Discov 2021; 11:971-994. [PMID: 33811127 PMCID: PMC8030695 DOI: 10.1158/2159-8290.cd-21-0010] [Citation(s) in RCA: 210] [Impact Index Per Article: 52.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 11/16/2022]
Abstract
Metastasis is initiated and sustained through therapy by cancer cells with stem-like and immune-evasive properties, termed metastasis-initiating cells (MIC). Recent progress suggests that MICs result from the adoption of a normal regenerative progenitor phenotype by malignant cells, a phenotype with intrinsic programs to survive the stresses of the metastatic process, undergo epithelial-mesenchymal transitions, enter slow-cycling states for dormancy, evade immune surveillance, establish supportive interactions with organ-specific niches, and co-opt systemic factors for growth and recurrence after therapy. Mechanistic understanding of the molecular mediators of MIC phenotypes and host tissue ecosystems could yield cancer therapeutics to improve patient outcomes. SIGNIFICANCE: Understanding the origins, traits, and vulnerabilities of progenitor cancer cells with the capacity to initiate metastasis in distant organs, and the host microenvironments that support the ability of these cells to evade immune surveillance and regenerate the tumor, is critical for developing strategies to improve the prevention and treatment of advanced cancer. Leveraging recent progress in our understanding of the metastatic process, here we review the nature of MICs and their ecosystems and offer a perspective on how this knowledge is informing innovative treatments of metastatic cancers.
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Affiliation(s)
- Joan Massagué
- Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, New York.
| | - Karuna Ganesh
- Molecular Pharmacology Program, Sloan Kettering Institute, New York, New York.
- Department of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, New York
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Farris AB, Vizcarra J, Amgad M, Cooper LAD, Gutman D, Hogan J. Artificial intelligence and algorithmic computational pathology: an introduction with renal allograft examples. Histopathology 2021; 78:791-804. [PMID: 33211332 DOI: 10.1111/his.14304] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Whole slide imaging, which is an important technique in the field of digital pathology, has recently been the subject of increased interest and avenues for utilisation, and with more widespread whole slide image (WSI) utilisation, there will also be increased interest in and implementation of image analysis (IA) techniques. IA includes artificial intelligence (AI) and targeted or hypothesis-driven algorithms. In the overall pathology field, the number of citations related to these topics has increased in recent years. Renal pathology is one anatomical pathology subspecialty that has utilised WSIs and IA algorithms; it can be argued that renal transplant pathology could be particularly suited for whole slide imaging and IA, as renal transplant pathology is frequently classified by use of the semiquantitative Banff classification of renal allograft pathology. Hypothesis-driven/targeted algorithms have been used in the past for the assessment of a variety of features in the kidney (e.g. interstitial fibrosis, tubular atrophy, inflammation); in recent years, the amount of research has particularly increased in the area of AI/machine learning for the identification of glomeruli, for histological segmentation, and for other applications. Deep learning is the form of machine learning that is most often used for such AI approaches to the 'big data' of pathology WSIs, and deep learning methods such as artificial neural networks (ANNs)/convolutional neural networks (CNNs) are utilised. Unsupervised and supervised AI algorithms can be employed to accomplish image or semantic classification. In this review, AI and other IA algorithms applied to WSIs are discussed, and examples from renal pathology are covered, with an emphasis on renal transplant pathology.
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Affiliation(s)
- Alton B Farris
- Department of Pathology and Laboratory Medicine, Atlanta, GA, USA
| | - Juan Vizcarra
- Department of Bioinformatics, Emory University, Atlanta, GA, USA
| | - Mohamed Amgad
- Department of Pathology and Center for Computational Imaging and Signal Analytics, Northwestern University, Chicago, IL, USA
| | - Lee A D Cooper
- Department of Pathology and Center for Computational Imaging and Signal Analytics, Northwestern University, Chicago, IL, USA
| | - David Gutman
- Department of Bioinformatics, Emory University, Atlanta, GA, USA
| | - Julien Hogan
- Department of Surgery, Emory University, Atlanta, GA, USA
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