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Sivamayuran V, Wijesinghe HD, Constantine R, Lokuhetty MDS. Tumor Budding in Invasive Breast Carcinoma, No Special Type: Association With Pathological Prognostic Factors and Comparison of 2 Different Scoring Systems. Int J Surg Pathol 2025; 33:309-317. [PMID: 39034045 DOI: 10.1177/10668969241260213] [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] [Indexed: 07/23/2024]
Abstract
Introduction. In contrast to colorectal carcinoma, the significance of tumor budding in breast carcinoma is not established. The X20 objective which is used to assess tumor budding in colorectal carcinoma, is not widely available in countries with limited resources. This study aimed to determine the prevalence of tumor budding and its associations with pathological prognostic factors in invasive breast carcinoma-no special type (IBC-NST), and to assess the correlation between the tumor budding observed using ×20 and ×40 objectives. Methods. A total of 349 excision specimens of IBC-NST were studied. Tumor budding was defined as a single cell/cluster of up to 4 cells at the invasive front and was assessed in hotspots at the advancing edge of the tumor using ×20 and ×40 objectives. Tumor budding was categorized into low (<5/0.785 mm2), intermediate (5-9/0.785 mm2), and high budding (≥10/0.785 mm2) for ×20 objective and low (≤4/0.196 mm2) and high (≥5/0.196 mm2) for ×40 objective based on the number of buds per hotspot. The association between tumor budding and prognostic factors was analyzed with Mann-Whitney U test, Kruskal-Wallis test, χ2 test, and logistic regression. Correlation between tumor budding in ×20 and ×40 objectives was analyzed with Pearson correlation test. Results. The prevalence of tumor budding was 72.5%. There was a significant correlation between the number of buddings observed in ×40 objective and ×20 objective (0.958). High tumor budding observed in both objectives was significantly associated with size (P < .001), lymphovascular invasion (P < .001), perineural invasion (P < .001), lymph node status (P < .001), number of lymph nodes (P < .001), T stage (P < .001), and N stage (P < .001) on univariate analysis, but only lymph node positivity (P < .001) showed significant association on multivariate analysis. Conclusion. Tumor budding assessed with ×20 and ×40 objectives showed a significant correlation and was significantly associated lymph node metastasis on multivariate analysis.
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King KL, Abdollahi H, Dinkel Z, Akins A, Valafar H, Dunn H. Pilot study: Initial investigation suggests differences in EMT-associated gene expression in breast tumor regions. Comput Struct Biotechnol J 2025; 27:548-555. [PMID: 39981295 PMCID: PMC11840942 DOI: 10.1016/j.csbj.2025.01.027] [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: 09/18/2024] [Revised: 01/29/2025] [Accepted: 01/29/2025] [Indexed: 02/22/2025] Open
Abstract
Triple negative breast cancer (TNBC) is the most aggressive subtype and disproportionately affects African American women. The development of breast cancer is highly associated with interactions between tumor cells and the extracellular matrix (ECM), and recent research suggests that cellular components of the ECM vary between racial groups. This pilot study aimed to evaluate gene expression in TNBC samples from patients who identified as African American and Caucasian using traditional statistical methods and emerging Machine Learning (ML) approaches. ML enables the analysis of complex datasets and the extraction of useful information from small datasets. We selected four regions of interest from tumor biopsy samples and used laser microdissection to extract tissue for gene expression characterization via RT-qPCR. Both parametric and non-parametric statistical analyses identified genes differentially expressed between the two ethnic groups. Out of 40 genes analyzed, 4 were differentially expressed in the edge of tumor (ET) region and 8 in the ECM adjacent to the tumor (ECMT) region. In addition to statistical approach, ML was used to generate decision trees (DT) for a broader analysis of gene expression and ethnicity. Our DT models achieved 83.33 % accuracy and identified the most significant genes, including CD29 and EGF from the ET region and SNAI1 and CHD2 from the ECMT region. All significant genes were analyzed for pathway enrichment using MSigDB and Gene Ontology databases, most notably the epithelial to mesenchymal transition and cell motility pathways. This pilot study highlights key genes of interest that are differentially expressed in African American and Caucasian TNBC samples.
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Affiliation(s)
- Kylie L. King
- Department of Bioengineering, Clemson University, Clemson, SC, USA
| | - Hamed Abdollahi
- Department of Computer Science and Engineering, University of South Carolina, Columbia, SC, USA
| | - Zoe Dinkel
- Department of Bioengineering, Clemson University, Clemson, SC, USA
| | - Alannah Akins
- Department of Bioengineering, Clemson University, Clemson, SC, USA
| | - Homayoun Valafar
- Department of Computer Science and Engineering, University of South Carolina, Columbia, SC, USA
| | - Heather Dunn
- Department of Bioengineering, Clemson University, Clemson, SC, USA
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Haas M, Engelmann SU, Mayr R, Gossler C, Pickl C, Kälble S, Yang Y, Otto W, Hartmann V, Burger M, Hartmann A, Breyer J, Eckstein M. A novel grading approach predicts worse outcomes in stage pT1 non-muscle-invasive bladder cancer. BJU Int 2024; 134:249-257. [PMID: 38409965 DOI: 10.1111/bju.16298] [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] [Indexed: 02/28/2024]
Abstract
OBJECTIVE To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. PATIENTS AND METHODS The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. RESULTS The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. CONCLUSIONS We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results.
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Affiliation(s)
- Maximilian Haas
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Simon U Engelmann
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Roman Mayr
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Christopher Gossler
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Christoph Pickl
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Sebastian Kälble
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Yushan Yang
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Wolfgang Otto
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Valerie Hartmann
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Maximilian Burger
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
| | - Johannes Breyer
- Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany
| | - Markus Eckstein
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
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Liu H, Lan T, Cai YS, Lyu YH, Zhu J, Xie SN, Hu FJ, Liu C, Wu H. Predicting prognosis in intrahepatic cholangiocarcinoma by the histopathological features. Asian J Surg 2024; 47:2589-2597. [PMID: 38604849 DOI: 10.1016/j.asjsur.2024.03.085] [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: 09/12/2023] [Revised: 12/23/2023] [Accepted: 03/06/2024] [Indexed: 04/13/2024] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous liver tumor. The associations between histopathological feature and prognosis of ICC are limited. The present study aimed to investigate the prognostic significance of glandular structure and tumor budding in ICC. METHODS Patients received radical hepatectomy for ICC were included. Glandular structure and tumor budding were detected by Hematoxylin-eosin staining. The Kaplan-Meier method and the Cox proportional hazards regression model were used to calculate the survival and hazard ratio. Based on the results of multivariate analysis, nomograms of OS and DFS were constructed. C-index and Akaike information criterion (AIC) were used to assess accuracy of models. RESULTS A total of 323 ICC patients who underwent surgery were included in our study. Glandular structure was associated with worse overall survival (OS) [hazard ratio (HR): 2.033, 95% confidence interval (CI): 1.047 to 3.945] and disease-free survival (DFS) [HR: 1.854, 95% CI: 1.082 to 3.176]. High tumor budding was associated with worse DFS [HR: 1.636, 95%CI: 1.060 to 2.525]. Multivariate analysis suggested that glandular structure, tumor number, lymph node metastasis, and CA19-9 were independent risk factors for OS. Independent predictor factors for DFS were tumor budding, glandular structure, tumor number, and lymph node metastasis. The c-index (0.641 and 0.642) and AIC (957.69 and 1188.52) showed that nomograms of OS and DFS have good accuracy. CONCLUSION High tumor budding and glandular structure are two important histopathological features that serve as prognostic factors for ICC patients undergoing hepatectomy.
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Affiliation(s)
- Hu Liu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tian Lan
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yun-Shi Cai
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ying-Hao Lyu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiang Zhu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Si-Nan Xie
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Feng-Juan Hu
- The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chang Liu
- Division of Liver, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Minimal Invasive Surgery, Shangjin Nanfu Hospital, Chengdu, 610037, China.
| | - Hong Wu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Ibuki E, Kadota K, Kimura N, Ishikawa R, Oshima M, Okano K, Haba R. Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy. Heliyon 2024; 10:e23928. [PMID: 38205326 PMCID: PMC10777074 DOI: 10.1016/j.heliyon.2023.e23928] [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: 07/09/2023] [Revised: 12/13/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024] Open
Abstract
Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm2) and at 40 × magnification (/0.237 mm2; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy.
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Affiliation(s)
- Emi Ibuki
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
| | - Kyuichi Kadota
- Molecular Oncologic Pathology, Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
| | - Nachino Kimura
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
| | - Ryou Ishikawa
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
| | - Minoru Oshima
- Departments of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
| | - Keiichi Okano
- Departments of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
| | - Reiji Haba
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
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Buch A, Khan U, Rathod H, Jain K, Dwivedi A, Rajesh A. Tumor budding in breast carcinoma: A systematic review and meta-analysis. J Cancer Res Ther 2023; 19:1697-1713. [PMID: 38376268 DOI: 10.4103/jcrt.jcrt_188_22] [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: 01/24/2022] [Accepted: 03/04/2022] [Indexed: 02/21/2024]
Abstract
ABSTRACT Tumor budding is gaining importance as a prognostic factor in various carcinomas due to its association with epithelial-mesenchymal transition (EMT) and hence clinical outcome. Reporting tumor budding in breast cancer lacks homogeneity. We aim to systematically review the existing literature and conduct a meta-analysis to assess the prognostic implication of tumor budding in breast carcinoma. A systematic search was performed to identify studies that compared different prognostic variables between high- and low-grade tumor budding. Quality assessment was performed using a modified Newcastle Ottawa Scale. Dichotomous variables were pooled using the odds ratio using the Der-Simonian-Laird method. Meta-analysis was conducted to study the association between low/high-grade tumor budding and tumor grade, lymph node metastasis, lymphovascular invasion, ER, PR, HER2neu, KI67, and the molecular subtype triple-negative breast carcinoma. Thirteen studies with a total of 1763 patients were included. A moderate risk of bias was noted. The median bias scoring was 7 (6-9). High-grade tumor budding was significantly associated with lymph node metastasis (OR: 2.25, 95% CI: 1.52-3.34, P < 0.01) and lymphovascular invasion (OR: 3.14, 95% CI: 2.10-4.71, P < 0.01), and low-grade budding was significantly associated with triple-negative breast carcinoma (OR: 0.61, 95% CI: 0.39-0.95, P = 0.03)There was significant heterogeneity in the assessment and grading of tumor budding; thus, a checklist of items was identified that lacked standardization. Our meta-analysis concluded that tumor budding can act as an independent prognostic marker for breast cancer.
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Affiliation(s)
- Archana Buch
- Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Uzair Khan
- Department of Undergraduate Students Section, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Hetal Rathod
- Department of Community Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Khushi Jain
- Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Aryan Dwivedi
- Department of Undergraduate Students Section, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Arasi Rajesh
- Department of Pathology, Tirunelveli Medical College, Tamil Nadu, India
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Ozer SP. Tumor budding in invasive breast carcinoma: correlation with clinicopathological parameters, hormone receptor status, and survival: an observational study. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2023; 69:e20230191. [PMID: 37792866 PMCID: PMC10547490 DOI: 10.1590/1806-9282.20230191] [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: 07/04/2023] [Accepted: 07/07/2023] [Indexed: 10/06/2023]
Abstract
OBJECTIVE Tumor budding is currently thought to be associated with worse prognosis. This study aims to examine tumor budding in invasive ductal-type breast carcinoma and its relationship with other clinicopathological parameters and overall survival. METHODS All the H&E slides of 198 patients were re-evaluated for the histological grade, angiolymphatic invasion, perineural invasion, lymph node status, extranodal extension, multicentricity, pT, presence of the tumor budding, tumor budding score (i.e., low, intermediate, or high). Overall survival was considered the period after surgery until death. SPSS was used for statistical analysis. RESULTS Tumor budding was identified in 98 (49.5%) patients. Tumor budding score was low in 41 (41.8%) of 98 cases, intermediate in 25 (25.5%), and high in 32 (32.7%). We determined a strong correlation between tumor budding and poor prognostic variables such as tumor size, pT stage, angiolymphatic invasion, perineural invasion, number of metastatic axillary lymph nodes, overall survival, and extranodal tumor extension in metastatic lymph nodes. This strong correlation was also present for the tumor budding score. CONCLUSION Tumor budding may be a prognostic indicator for breast cancer.
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Affiliation(s)
- Songul Peltek Ozer
- Bolu Abant Izzet Baysal Training and Research Hospital, Department of Pathology – Bolu, Turkey
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Savli TB, Pasaoglu HE, Savli TC, Muhammedoglu A, Tokocin M, Öztürk Ç. Expression of cytotoxic T lymphocyte-associated antigen 4, CD44, and E-cadherin in the microenvironment of breast carcinomas. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2023; 69:e20230371. [PMID: 37466609 PMCID: PMC10351999 DOI: 10.1590/1806-9282.20230371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 04/28/2023] [Indexed: 07/20/2023]
Abstract
OBJECTIVE The expression of cytotoxic T lymphocyte-associated antigen 4, E-cadherin, and CD44 in the area of tumor budding was investigated in breast carcinomas in our study. METHODS Tumor budding was counted at the invasive margins in 179 breast carcinomas. To understand the microenvironment of tumor budding, we examined the expression status of the immune checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4, E-cadherin, and CD44. RESULTS Tumors were separated into low (≤5) and high tumor budding groups (>5) based on the median budding number. Lymphovascular, perineural invasion, and the number of metastatic lymph nodes were significantly higher in high-grade budding tumors (p=0.001, p<0.001, and p=0.019, respectively). Tumor-infiltrating lymphocytes were significantly higher in tumors without tumor buddings (p<0.001). When the number of budding increases by one unit, overall survival decreases by 1.07 times (p=0.013). Also, it increases the risk of progression by 1.06 times (p=0.048). In high tumor budding groups, the cytotoxic T lymphocyte-associated antigen 4 staining percentage of lymphocytes was significantly higher (p=0.026). With each increase in the number of buds, an increase in the percentage of cytotoxic T lymphocyte-associated antigen 4 staining was seen in lymphocytes in the microenvironment of TB (p=0.034). CONCLUSION Tumor budding could predict poor prognosis in breast carcinomas, and anti-cytotoxic T lymphocyte-associated antigen 4 immunotherapies may be beneficial in patients with high tumor budding tumors.
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Affiliation(s)
- Tugce Bolme Savli
- Gaziantep Cengiz Gokcek Maternity and Child Health Hospital, Department of Pathology - Gaziantep, Turkey
| | - Husniye Esra Pasaoglu
- Istanbul Bagcilar Training and Research Hospital, Department of Pathology - Istanbul, Turkey
| | - Taha Cumhan Savli
- Medipol Mega University Hospital, Department of Pathology - Istanbul, Turkey
| | - Ali Muhammedoglu
- Istanbul Bagcilar Training and Research Hospital, Department of Pathology - Istanbul, Turkey
| | - Merve Tokocin
- Istanbul Bagcilar Training and Research Hospital, Department of General Surgery - Istanbul, Turkey
| | - Çiğdem Öztürk
- Recep Tayyip Erdoğan University Training and Research Hospital, Pathology Department - Rize, Turkey
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Zenger S, Gurbuz B, Can U, Erginoz E, Ozata IH, Yilmaz SP, Taskin OC, Peker O, Adsay V, Balik E, Bugra D. Is there no need to discuss adjuvant chemotherapy in stage II colon cancer patients with high tumor budding and lymphovascular invasion? Langenbecks Arch Surg 2023; 408:127. [PMID: 36973561 DOI: 10.1007/s00423-023-02864-x] [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: 07/06/2022] [Accepted: 03/13/2023] [Indexed: 03/29/2023]
Abstract
PURPOSE The aim of this study is to evaluate the clinicopathologic associations of tumor budding (Bd) as well as other potential prognosticators including lymphovascular invasion (LVI) in T3/4aN0 colon cancer patients and to investigate their impact on the outcome. METHODS The patients were enrolled in three groups according to the number of budding as Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (> 10 buds). These groups were retrospectively compared in terms of demographic features, other tumor characteristics, operative outcomes, recurrences, and survival. The mean follow-up time was 58 ± 22 months. RESULTS A total of 194 patients were divided as follows: 97 in Bd1, 41 in Bd2, and 56 in Bd3 groups. The Bd3 group was associated with significantly higher LVI and larger tumor size. The rate of recurrence increased progressively from 5.2% in Bd1 to 9.8% in Bd2 and to 17.9% in Bd3 group (p = 0.03). More importantly, the 5-year overall survival (OS: Bd1 = 92.3% vs. Bd2 = 88% vs. Bd3 = 69.5%, p = 0.03) and disease-free survival (DFS: Bd1 = 87.9% vs. Bd2 = 75.3% vs. Bd3 = 66%, p = 0.02) were significantly worse in Bd3 group. In addition, in the subgroup of patients with the presence of Bd3 and LVI together, the 5-year OS (60% vs. 92%, p = 0.001) and DFS (56.1% vs. 85.4%, p = 0.001) were significantly worse. In multivariate analysis, Bd3+LVI was significantly associated with poor OS and DFS (p < 0.001). CONCLUSION In patients with T3/4aN0 colon cancer, high tumor budding negatively affects long-term oncological outcomes. These findings strongly suggest that adjuvant chemotherapy be considered for the patients with Bd3 and LVI together.
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Affiliation(s)
- Serkan Zenger
- Department of General Surgery, VKF American Hospital, Istanbul, Turkey.
| | - Bulent Gurbuz
- Department of General Surgery, VKF American Hospital, Istanbul, Turkey
| | - Ugur Can
- Department of General Surgery, VKF American Hospital, Istanbul, Turkey
| | - Ergin Erginoz
- Department of General Surgery, Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey
| | - Ibrahim Halil Ozata
- Department of General Surgery, Koç University, School of Medicine, Istanbul, Turkey
| | | | - Orhun Cıg Taskin
- Department of Pathology, Koç University, School of Medicine, Istanbul, Turkey
| | - Onder Peker
- Department of Pathology, VKF American Hospital, Istanbul, Turkey
| | - Volkan Adsay
- Department of Pathology, Koç University, School of Medicine, Istanbul, Turkey
| | - Emre Balik
- Department of General Surgery, Koç University, School of Medicine, Istanbul, Turkey
| | - Dursun Bugra
- Department of General Surgery, VKF American Hospital, Istanbul, Turkey
- Department of General Surgery, Koç University, School of Medicine, Istanbul, Turkey
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Does the number of cell forming tumor budding alter the prognostic value in invasive ductal carcinoma of breast? Pathol Res Pract 2022; 240:154157. [DOI: 10.1016/j.prp.2022.154157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/03/2022] [Accepted: 10/04/2022] [Indexed: 11/06/2022]
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Shi H, Ye L, Lu W, Lu B. Grading of endocervical adenocarcinoma: a novel prognostic system based on tumor budding and cell cluster size. Mod Pathol 2022; 35:524-532. [PMID: 34593968 DOI: 10.1038/s41379-021-00936-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/16/2021] [Accepted: 09/16/2021] [Indexed: 11/09/2022]
Abstract
A novel 3-tiered grading system based on tumor budding activity and cell nest size has been validated to be highly prognostic in organ-wide squamous cell carcinomas. In this study, we applied a similar grading system with slight modification to assess the prognostic value in an institutional cohort of well annotated endocervical adenocarcinomas (EAC) consisting of 398 consecutive cases with surgical resection, no neoadjuvant chemotherapy, and higher than stage pT1a. Each case was reviewed by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and Silva pattern classification, and scored on tumor budding activity and cell cluster size to form the basis of a novel grading system. High budding activity, small tumor cell cluster size, and novel grade 3 were more frequently associated with a decreased overall survival time and tumor recurrence time (p < 0.001), and several other clinicopathologic factors including HPV-independent adenocarcinoma, lymphovascular invasion, lymph node metastasis, advanced FIGO stage, and Silva pattern C (p < 0.05). Moreover, the novel grading system was helpful in stratifying overall survival in HPV-associated adenocarcinoma (p = 0.036) and gastric-type adenocarcinoma (p = 0.033). On multivariate analysis, novel grade 3 was an adverse indicator for overall survival and tumor recurrence independently of age and FIGO stage (p < 0.05). By comparison, Silva pattern C was only associated with tumor relapse (p = 0.020) in HPV-associated adenocarcinomas whereas the conventional FIGO system was not associated with overall survival and tumor recurrence in EAC (p > 0.05). In conclusion, our study demonstrates that the grading system based on tumor budding activity and cell cluster size is robust in prognostic assessment that outperforms the conventional FIGO grading and Silva pattern classification in EAC. The novel grading system, if further validated, could be applicable in routine pathologic descriptions of EAC by providing useful information in clinical decision-making.
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Affiliation(s)
- Haiyan Shi
- Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Lei Ye
- Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Weiguo Lu
- Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province and Department of Gynecological Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Bingjian Lu
- Department of Surgical Pathology and Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
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12
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Nguyen TTA, Postlewait LM, Zhang C, Meisel JL, O'Regan R, Badve S, Kalinsky K, Li X. Utility of Oncotype DX score in clinical management for T1 estrogen receptor positive, HER2 negative, and lymph node negative breast cancer. Breast Cancer Res Treat 2022; 192:509-516. [PMID: 35084624 DOI: 10.1007/s10549-022-06530-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 01/17/2022] [Indexed: 12/16/2022]
Abstract
BACKGROUND The management of estrogen receptor positive (ER+)/HER2- and lymph node (LN) negative breast cancers can be influenced by Oncotype DX recurrence score (RS) in the USA. However, the benefit of RS in T1 tumors (≤ 1 cm) is not clear. METHODS We retrieved 199 T1 ER+/HER2-/LN- breast cancer diagnosed between 1993 and 2016 that had undergone RS testing. The median follow-up time was 51 months. We examined the disease-free survival (DFS) and distant metastasis and their association with RS and other clinicopathologic features. RESULTS Of the 199 cases, 40 were T1a (≤ 0.5 cm) and 159 were T1b (> 0.5 cm to 1 cm) tumors. In the 40 T1a tumors, 11 would benefit from chemotherapy by the TAILORx study results. Of these T1a tumors, 36 were Nottingham grade 1/2, 3 were grade 3, and 1 was microinvasive carcinoma; 2 (5%) had local recurrence and 1 (2.5%) had distant metastasis to the bone. The only patient with T1a tumor (Nottingham grade 3, RS = 42) and distant metastasis to bone had received adjuvant chemotherapy. In the 159 T1b tumors, 25 would benefit chemotherapy by the TAILORx results. Of the T1b tumors, 149 were Nottingham grade 1/2 and 10 were grade 3. Nine (5.7%) had local recurrence and 2 (1.3%) had distant metastasis to bone and mediastinum, respectively. The two T1b tumors with distant metastasis had a RS 20 and Nottingham grade 2, and RS 27 and Nottingham grade 3, respectively. Both patients received adjuvant chemotherapy. In multivariate analysis of the entire cohort (T1a and T1b tumors), Nottingham tumor grade and receiving chemotherapy were significantly associated with DFS. In univariate analysis of the entire cohort, Nottingham tumor grade, receiving adjuvant chemotherapy, and RS were significantly associated with distant metastasis. CONCLUSION This study demonstrates that the metastatic rate of T1a and T1b ER+/HER2-/LN- breast cancer is very low. Patients with low grade (1 or 2), T1a ER+/HER2-/LN- breast cancer may not need RS for treatment decision-making; however, in patients with high-grade T1a or T1b ER+/HER2-/LN- breast cancer, RS analysis should be strongly considered.
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Affiliation(s)
- Thi Truc Anh Nguyen
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | - Chao Zhang
- Pediatric Biostatistics Core, Department of Pediatrics, Emory University, Atlanta, GA, USA
| | - Jane L Meisel
- Department of Hematology and Oncology, Emory University, Atlanta, GA, USA
| | - Ruth O'Regan
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Sunil Badve
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Kevin Kalinsky
- Department of Hematology and Oncology, Emory University, Atlanta, GA, USA
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
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13
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Hiratsuka M, Hasebe T, Ichinose Y, Sakakibara A, Fujimoto A, Wakui N, Shibasaki S, Hirasaki M, Yasuda M, Nukui A, Shimada H, Yokogawa H, Matsuura K, Hojo T, Osaki A, Saeki T. Tumor budding and fibrotic focus-proposed grading system for tumor budding in invasive carcinoma no special type of the breast. Virchows Arch 2022; 481:161-190. [PMID: 35695928 PMCID: PMC9343319 DOI: 10.1007/s00428-022-03337-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 04/18/2022] [Accepted: 05/05/2022] [Indexed: 01/04/2023]
Abstract
Tumor budding grade is a very useful histological prognostic indicator for colorectal cancer patients. Recently, it has been also reported as a significant prognostic indicator in invasive breast carcinoma patients. Our group and others have previously reported that the presence of a fibrotic focus in the tumor is a very useful histological finding for accurately predicting the prognosis in patients with invasive carcinoma of no special type (ICNST) of the breast. The purpose of the present study was to investigate whether a grading system incorporating tumor budding in a fibrotic focus is superior to the conventional grading system for tumor budding to accurately predict outcomes in patients with ICNST. According to our new grading system, we classified the tumors into grade I (164 cases), grade II (581 cases), and grade III (110 cases), and the results clearly demonstrated the significant superiority of the new grading system over that of conventional tumor budding alone for accurately predicting outcomes in patients with ICNST. Our findings strongly suggest that tumor cells and tumor-stromal cells interaction play very important roles in tumor progression rather than tumor cells alone.
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Affiliation(s)
- Miyuki Hiratsuka
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Takahiro Hasebe
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Yuki Ichinose
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Ayaka Sakakibara
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Akihiro Fujimoto
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Noriko Wakui
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Satomi Shibasaki
- Community Health Science Center, Saitama Medical University, 29, Morohongou, Moroyama Town, Iruma district, Saitama 350-0495 Japan
| | - Masataka Hirasaki
- Department of Clinical Cancer Genomics, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Masanori Yasuda
- Department of Pathology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Akemi Nukui
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Hiroko Shimada
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Hideki Yokogawa
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Kazuo Matsuura
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Takashi Hojo
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Akihiko Osaki
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
| | - Toshiaki Saeki
- Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama 350-1298 Japan
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14
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Eckstein M, Kimmel C, Bruendl J, Weber F, Denzinger S, Gierth M, Burger M, Hartmann A, Otto W, Breyer J. Tumor budding correlates with tumor invasiveness and predicts worse survival in pT1 non-muscle-invasive bladder cancer. Sci Rep 2021; 11:17981. [PMID: 34504238 PMCID: PMC8429693 DOI: 10.1038/s41598-021-97500-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 08/23/2021] [Indexed: 12/24/2022] Open
Abstract
Tumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p < 0.001) and extensive lamina propria invasion (p < 0.001). In Kaplan-Meier analysis, tumor budding was associated with significantly worse RFS (p = 0.005), PFS (p = 0.017) and CSS (p = 0.002). In patients who received BCG instillation therapy (n = 65), the absence of tumor budding was associated with improved RFS (p = 0.012), PFS (p = 0.011) and CSS (p = 0.022), with none of the patients suffering from progression or dying from the disease. Tumor budding is associated with a more aggressive and invasive stage of pT1 NMIBC and a worse outcome. This easy-to-assess parameter could help stratify patients into BCG therapy or early cystectomy treatment groups.
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Affiliation(s)
- Markus Eckstein
- Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany
| | - Charlotte Kimmel
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Johannes Bruendl
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Florian Weber
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Stefan Denzinger
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Michael Gierth
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Maximilian Burger
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Arndt Hartmann
- Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany
| | - Wolfgang Otto
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Johannes Breyer
- Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Landshuter Str. 65, 93053, Regensburg, Germany.
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15
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Okcu O, Öztürk Ç, Şen B, Arpa M, Bedir R. Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters. Ann Diagn Pathol 2021; 54:151792. [PMID: 34293708 DOI: 10.1016/j.anndiagpath.2021.151792] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/18/2021] [Accepted: 07/11/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVE Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases. MATERIALS AND METHODS 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed. RESULTS We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis. CONCLUSION Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.
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Affiliation(s)
- Oğuzhan Okcu
- Recep Tayyip Erdoğan University Training and Research Hospital, Department of Pathology, Turkey.
| | - Çiğdem Öztürk
- Recep Tayyip Erdoğan University Training and Research Hospital, Department of Pathology, Turkey
| | - Bayram Şen
- Recep Tayyip Erdoğan University Training and Research Hospital, Department of Biochemistry, Turkey
| | - Medeni Arpa
- Recep Tayyip Erdoğan University, Faculty of Medicine, Department of Medical Biochemistry, Turkey
| | - Recep Bedir
- Recep Tayyip Erdoğan University, Faculty of Medicine, Department of Pathology, Turkey
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16
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Seker NS, Tekin E, Özen A, Can C, Colak E, Acikalin MF. Prognostic significance of tumor budding in muscle invasive urothelial carcinomas of the urinary bladder. Ann Diagn Pathol 2021; 54:151786. [PMID: 34229152 DOI: 10.1016/j.anndiagpath.2021.151786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/08/2021] [Accepted: 06/30/2021] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The aim of the present study was to analyze the prognostic significance of tumor budding in muscle-invasive urothelial carcinomas of the urinary bladder, and also to determine an optimal threshold value in evaluation. PATIENTS AND METHODS The study included 108 patients diagnosed with muscleinvasive conventional urothelial carcinoma between 2010 and 2020. Tumor budding was evaluated on H&E-stained slides. The critical tumor budding number was determined with the "receiver operating characteristics (ROC)" curve. Cases with a tumor budding number of ≤6 were categorized as low, and cases with >6 as high tumor budding. RESULTS The univariate Cox proportional hazards regression model for recurrence-free survival showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.012), pT stage (T4 vs. T2) (P = 0.005), and lymph node metastasis (P = 0.009) were significantly associated with recurrence-free survival. The multivariate Cox proportional hazards regression model utilizing backward stepwise (wald) method revealed that only LVI (P = 0.001) was independent risk factor for recurrence-free survival. The univariate Cox analysis showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.004), pT stage (T4 vs. T2) (P = 0.003), and lymph node metastasis (P = 0.001) were significantly associated with overall survival. The multivariate Cox analysis (backward stepwise (wald) method) revealed that tumor focality (P = 0.018), pT stage (T4 vs. T2) (P = 0.015), and lymphovascular invasion (P = 0.002) were independent factors for overall survival. CONCLUSIONS Our findings suggested that the evaluation of tumor budding may be a useful parameter for predicting outcome in patients with muscle-invasive bladder cancer.
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Affiliation(s)
- Nazlı Sena Seker
- Department of Pathology, Eskişehir Osmangazi University Faculty of Medicine, Meşelik Campus, 26480 Eskişehir, Turkey.
| | - Emel Tekin
- Department of Pathology, Eskişehir Osmangazi University Faculty of Medicine, Meşelik Campus, 26480 Eskişehir, Turkey
| | - Ata Özen
- Department of Urology, Eskişehir Osmangazi University Faculty of Medicine, Meşelik Campus, 26480 Eskişehir, Turkey
| | - Cavit Can
- Department of Urology, Eskişehir Osmangazi University Faculty of Medicine, Meşelik Campus, 26480 Eskişehir, Turkey
| | - Ertugrul Colak
- Department of Biostatistics, Eskişehir Osmangazi University Faculty of Medicine, Meşelik Campus, 26480 Eskişehir, Turkey
| | - Mustafa Fuat Acikalin
- Department of Pathology, Eskişehir Osmangazi University Faculty of Medicine, Meşelik Campus, 26480 Eskişehir, Turkey
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17
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Mozarowski P, Rasaiah B, Reed M, Lewis A, Walde N, Voutsadakis IA. Prognostic Role of Tumor Budding in Breast Cancer Patients Receiving Neo-Adjuvant Therapy. J Clin Med 2021; 10:jcm10040827. [PMID: 33670512 PMCID: PMC7922902 DOI: 10.3390/jcm10040827] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 02/11/2021] [Accepted: 02/13/2021] [Indexed: 11/26/2022] Open
Abstract
Background: Isolated tumor cells or small clusters of tumor cells observed in the vicinity of the main tumor mass in pathology sections, termed tumor budding, are common in cancers and have been associated with prognosis in some settings. This study examined the clinical associations and treatment efficacy implications of tumor budding in breast cancer patients receiving neo-adjuvant therapy. Methods: Breast cancer patients that received neo-adjuvant therapy before definitive surgical treatment in a single cancer center over a 7-year period were included, and their records were reviewed. Data extracted included patient demographics, tumor characteristics and pathologic response to treatment at surgery. The initial breast cancer biopsy before any therapy was reviewed by two pathologists, and a hot spot area was evaluated for tumor budding (defined as 1 to 5 cancer cells observed detached from the main tumor mass). Results: Seventy-five patients who received neo-adjuvant therapy (73 received chemotherapy and 2 received hormonal therapy) were included. Tumor budding was observed in two-thirds of the patients. There were no significant differences in patient (age and menopause status) and tumor (stage, histology and molecular sub-type equivalent) characteristics between the group that had tumor budding and the group that did not have tumor budding in the pre-treatment biopsy. Likewise, no statistically significant differences were observed in the frequency of complete or partial responses between the two groups. Conclusion: In this cohort of breast cancer patients receiving neo-adjuvant therapy, tumor budding was frequent, but it was not associated with tumor characteristics or pathologic responses to treatment. The value of tumor budding as a prognostic factor in the neo-adjuvant setting within the general breast cancer population could not be confirmed, but such a value in specific sub-groups deserves further investigation, given the pathophysiologic rationale and data from other settings.
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Affiliation(s)
- Paul Mozarowski
- Department of Pathology, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada; (P.M.); (B.R.)
| | - Bhubendra Rasaiah
- Department of Pathology, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada; (P.M.); (B.R.)
| | - Melissa Reed
- Clinical Trials Unit, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada; (M.R.); (A.L.); (N.W.)
- Faculty of Medicine, University of Ottawa School of Medicine, Ottawa, ON KK1H 8M5, Canada
| | - Alexis Lewis
- Clinical Trials Unit, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada; (M.R.); (A.L.); (N.W.)
- Department of Biology, Algoma University, Sault Ste. Marie, ON P6A 2G4, Canada
| | - Natalie Walde
- Clinical Trials Unit, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada; (M.R.); (A.L.); (N.W.)
| | - Ioannis A. Voutsadakis
- Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada
- Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada
- Correspondence:
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18
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González LO, Eiro N, Fraile M, Sánchez R, Andicoechea A, Fernández-Francos S, Schneider J, Vizoso FJ. Joint Tumor Bud-MMP/TIMP Count at the Invasive Front Improves the Prognostic Evaluation of Invasive Breast Carcinoma. Biomedicines 2021; 9:biomedicines9020196. [PMID: 33669393 PMCID: PMC7920253 DOI: 10.3390/biomedicines9020196] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/12/2021] [Accepted: 02/13/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Tumor budding is a histological phenomenon consisting of the formation of small clusters of one to five undifferentiated malignant cells detached from the main tumor mass which are observed in the tumor stroma. In the present study, we investigated the prognostic significance of tumor budding in breast cancer and its relationship with the expressions of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs). METHODS The number of buds was counted in whole-tissue sections from 153 patients with invasive ductal carcinomas who underwent a long follow-up period. In addition, an immunohistochemical study of MMP-9, -11, and -14 TIMP-1 and -2 expression by cell types at the invasive tumor front was carried out. RESULTS There was a wide variability in the number of buds among tumors, ranging from 0 to 28 (median = 5). Tumor budding count ≥ 4 was the optimal cut-off to predict both relapse-free and overall survival. High-grade tumor budding was associated with MMP/TIMP expression by cancer-associated fibroblasts. In addition, we found that the combination of tumor budding grade with MMP/TIMP expression by stromal cells, and especially with MMP-11 expression by mononuclear inflammatory cells, significantly improved the prognostic evaluation. CONCLUSION High-grade tumor budding is associated with a more aggressive tumor phenotype, which, combined with MMP/TIMP expression by stromal cells at the invasive front of the tumor, identifies patients with poor prognosis.
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Affiliation(s)
- Luis O. González
- Department of Anatomical Pathology, Fundación Hospital de Jove, 33290 Gijón, Spain;
| | - Noemi Eiro
- Research Unit, Fundación Hospital de Jove, 33290 Gijón, Spain; (N.E.); (M.F.); (S.F.-F.)
| | - María Fraile
- Research Unit, Fundación Hospital de Jove, 33290 Gijón, Spain; (N.E.); (M.F.); (S.F.-F.)
| | - Rosario Sánchez
- Department of Surgery, Fundación Hospital de Jove, 33290 Gijón, Spain; (R.S.); (A.A.)
| | - Alejandro Andicoechea
- Department of Surgery, Fundación Hospital de Jove, 33290 Gijón, Spain; (R.S.); (A.A.)
| | | | - Jose Schneider
- Department of Obstetrics and Gynecology, University of Valladolid, 47005 Valladolid, Spain;
| | - Francisco J. Vizoso
- Research Unit, Fundación Hospital de Jove, 33290 Gijón, Spain; (N.E.); (M.F.); (S.F.-F.)
- Department of Surgery, Fundación Hospital de Jove, 33290 Gijón, Spain; (R.S.); (A.A.)
- Correspondence: ; Tel.: +34-9-8532-0050 (ext. 84216); Fax: +34- 9-8531-5710
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19
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Zhao J, Meisel J, Guo Y, Nahta R, Hsieh KL, Peng L, Wei Z, O'Regan R, Li X. Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies. Breast Cancer Res Treat 2020; 183:599-606. [PMID: 32715443 DOI: 10.1007/s10549-020-05819-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 07/17/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy. METHODS We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate. RESULTS Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096). CONCLUSIONS High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.
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Affiliation(s)
- Jing Zhao
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jane Meisel
- Department of Hematology and Oncology, Emory University, Atlanta, GA, USA
| | - Yi Guo
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Rita Nahta
- Department of Pharmacology, Emory University, Atlanta, GA, USA
| | - Kung Lin Hsieh
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA
| | - Limin Peng
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Zhimin Wei
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ruth O'Regan
- Department of Medicine, University of Wisconsin, Madison, WI, USA
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA.
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20
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The histopathological and molecular features of breast carcinoma with tumour budding-a systematic review and meta-analysis. Breast Cancer Res Treat 2020; 183:503-514. [PMID: 32710280 DOI: 10.1007/s10549-020-05810-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 07/15/2020] [Indexed: 01/04/2023]
Abstract
PURPOSE Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. METHODS A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). CONCLUSION High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.
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21
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Tumour budding and its clinical implications in gastrointestinal cancers. Br J Cancer 2020; 123:700-708. [PMID: 32601463 PMCID: PMC7462864 DOI: 10.1038/s41416-020-0954-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 04/17/2020] [Accepted: 06/02/2020] [Indexed: 02/07/2023] Open
Abstract
Tumour budding in colorectal cancer has become an important prognostic factor. Represented by single cells or small tumour cell clusters at the invasion front of the tumour mass, these tumour buds seem to reflect cells in a ‘hybrid’ state of epithelial–mesenchymal transition, and evidence indicates that the presence of these entities is associated with lymph node metastasis, local recurrence and distant metastatic disease. The International Tumour Budding Consensus Conference (ITBCC) has highlighted a scoring system for the reporting of tumour budding in colorectal cancer, as well as different clinical scenarios that could affect patient management. Other organs are not spared: tumour budding has been described in numerous gastrointestinal and non-gastrointestinal cancers. Here, we give an update on ITBCC validation studies in the context of colorectal cancer and the clinical implications of tumour budding throughout the upper gastrointestinal and pancreatico-biliary tract.
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22
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Fauzi MFA, Chen W, Knight D, Hampel H, Frankel WL, Gurcan MN. Tumor Budding Detection System in Whole Slide Pathology Images. J Med Syst 2019; 44:38. [PMID: 31853654 DOI: 10.1007/s10916-019-1515-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 12/12/2019] [Indexed: 02/06/2023]
Abstract
Tumor budding is defined as the presence of single tumor cells or small tumor clusters (less than five cells) that 'bud' from the invasive front of the main tumor. Tumor budding (TB) has recently emerged as an important adverse prognostic factor for many different cancer types. In colorectal carcinoma (CRC), tumor budding has been independently associated with lymph node metastasis and poor outcome. Pathologic assessment of tumor budding by light microscopy requires close evaluation of tumor invasive front on intermediate to high power magnification, entailing locating the 'hotspot' of tumor budding, counting all TB in one high power field, and generating a tumor budding score. By automating these time-consuming tasks, computer-assisted image analysis tools can be helpful for daily pathology practice, since tumor budding reporting is now recommended on select cases. In this paper, we report our work on the development of a tumor budding detection system in CRC from whole-slide Cytokeratin AE1/3 images, based on de novo computer algorithm that automates morphometric analysis of tumor budding.
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Affiliation(s)
- Mohammad F A Fauzi
- Faculty of Engineering, Multimedia University, 63100, Cyberjaya, SGR, Malaysia.
| | - Wei Chen
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Debbie Knight
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Heather Hampel
- Department of Internal Medicine, Division of Human Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Wendy L Frankel
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Metin N Gurcan
- Center for Biomedical Informatics, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA
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23
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24
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Almangush A, Youssef O, Pirinen M, Sundström J, Leivo I, Mäkitie AA. Does evaluation of tumour budding in diagnostic biopsies have a clinical relevance? A systematic review. Histopathology 2019; 74:536-544. [PMID: 30450728 DOI: 10.1111/his.13793] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Tumour budding has emerged as a promising prognostic marker in many cancers. We systematically reviewed all studies that evaluated tumour budding in diagnostic biopsies. We conducted a systematic review of PubMed, MEDLINE, Scopus, Web of Science and Cochrane library for all articles that have assessed tumour budding in diagnostic (i.e. pretreatment or pre-operative) biopsies of any tumour type. Two independent researchers screened the retrieved studies, removed duplicates, excluded irrelevant studies and extracted data from the eligible studies. A total of 13 reports comprising 11 cohorts were found to have studied tumour budding in diagnostic biopsies. All these reports showed that evaluation of tumour budding in diagnostic biopsies was easily applicable. A strong association was observed between tumour budding score in diagnostic biopsies and corresponding surgical samples. Evaluation of tumour budding in diagnostic biopsies had a significant prognostic value for lymph node metastasis and patient survival. In all studies, tumour budding was a valuable marker of tumour aggressiveness and can be evaluated in technically satisfactory diagnostic biopsies. Thus, the assessment of tumour budding seems to identify the behaviour of cancer, and therefore to facilitate treatment planning.
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Affiliation(s)
- Alhadi Almangush
- Department of Pathology, University of Helsinki, Helsinki, Finland.,Pathology, Institute of Biomedicine, University of Turku, Turku, Finland.,Institute of Dentistry, University of Misurata, Misurata, Libya
| | - Omar Youssef
- Department of Pathology, University of Helsinki, Helsinki, Finland
| | - Matti Pirinen
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.,Department of Public Health, University of Helsinki, Helsinki, Finland.,Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
| | - Jari Sundström
- Pathology, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Ilmo Leivo
- Pathology, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Antti A Mäkitie
- Department of Otorhinolaryngology - Head and Neck Surgery, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland.,Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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25
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Karpathiou G, Vieville M, Gavid M, Camy F, Dumollard JM, Magné N, Froudarakis M, Prades JM, Peoc'h M. Prognostic significance of tumor budding, tumor‐stroma ratio, cell nests size, and stroma type in laryngeal and pharyngeal squamous cell carcinomas. Head Neck 2019; 41:1918-1927. [PMID: 30620425 DOI: 10.1002/hed.25629] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 12/08/2018] [Accepted: 12/19/2018] [Indexed: 12/30/2022] Open
Affiliation(s)
- Georgia Karpathiou
- Department of PathologyNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Marine Vieville
- Department of Head and Neck SurgeryNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Marie Gavid
- Department of Head and Neck SurgeryNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Florian Camy
- Department of PathologyNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Jean Marc Dumollard
- Department of PathologyNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Nicolas Magné
- Radiotherapy DepartmentLucien Neuwirth Cancer Institute Saint‐Etienne France
| | - Marios Froudarakis
- Department of Pneumology and Thoracic OncologyNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Jean Michel Prades
- Department of Head and Neck SurgeryNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
| | - Michel Peoc'h
- Department of PathologyNorth Hospital, University Hospital of Saint‐Etienne Saint‐Etienne France
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26
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Boxberg M, Bollwein C, Jöhrens K, Kuhn PH, Haller B, Steiger K, Wolff KD, Kolk A, Jesinghaus M, Weichert W. Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance. J Clin Pathol 2018; 72:285-294. [PMID: 30530818 DOI: 10.1136/jclinpath-2018-205454] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 10/31/2018] [Accepted: 11/10/2018] [Indexed: 01/23/2023]
Abstract
AIMS Squamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading scheme strongly associated with patient outcome in OSCC, consisting of a sum score of the histomorphological patterns tumour budding and cell nest size which outperforms WHO based grading algorithms currently in use. The aim of our study was to probe for interobserver and intraobserver reliability of this novel grading system. METHODS 108 OSCC were retrospectively scored according to the proposed grading scheme by three independent pathologists-two experienced head and neck pathologists and one pathologist in training-blinded to each other's scoring results. RESULTS The Cohen's Kappa (κ) values for concordance rates between experienced pathologists were κ=0.97 for the overall grade, κ=0.97 for budding activity and κ=0.91 for cell nest size, indicating a strong interobserver reliability of our proposed grading system. Initial interobserver agreement was markedly lower with the pathologist in training (κ=0.55 for overall grade) but improved significantly after a training session (κ=0.87 for overall grade). Intraobserver concordance was high (κ=0.95 for overall grade), indicating a high reproducibility of the algorithm. CONCLUSIONS In conclusion, our study indicates that OSCC grading based on our proposed novel scheme yields an excellent inter-reader and intrareader agreement, further supporting the suitability of this grading system for routine pathological practice.
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Affiliation(s)
- Melanie Boxberg
- Institute of Pathology, Technical University of Munich (TUM), Munich, Germany
| | - Christine Bollwein
- Institute of Pathology, Technical University of Munich (TUM), Munich, Germany
| | - Korinna Jöhrens
- Institute of Pathology, University Carl Gustav Carus, Dresden, Germany
| | - Peer-Hendrik Kuhn
- Institute of Pathology, Technical University of Munich (TUM), Munich, Germany
| | - Bernhard Haller
- Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich (TUM), Munich, Germany
| | - Katja Steiger
- Institute of Pathology, Technical University of Munich (TUM), Munich, Germany
| | - Klaus-Dietrich Wolff
- Department of Oral- and Maxillofacial Surgery, Klinikum Rechts der Isar, Munich, Germany
| | - Andreas Kolk
- Department of Oral- and Maxillofacial Surgery, Klinikum Rechts der Isar, Munich, Germany
| | - Moritz Jesinghaus
- Institute of Pathology, Technical University of Munich (TUM), Munich, Germany.,German Cancer Consortium (DKTK), Munich, Germany
| | - Wilko Weichert
- Institute of Pathology, Technical University of Munich (TUM), Munich, Germany.,German Cancer Consortium (DKTK), Munich, Germany
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27
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Ren Z, Yang T, Zhang P, Liu K, Liu W, Wang P. SKA2 mediates invasion and metastasis in human breast cancer via EMT. Mol Med Rep 2018; 19:515-523. [PMID: 30387823 DOI: 10.3892/mmr.2018.9623] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Accepted: 10/02/2018] [Indexed: 11/06/2022] Open
Abstract
Spindle and kinetochore‑associated protein 2 (SKA2) is essential for regulating the progression of mitosis. In recent years, SKA2 upregulation has been detected in various human malignancies and the role of SKA2 in tumorigenesis has received increasing attention. However, the expression and functional significance of SKA2 in breast cancer are not completely understood. To study the effects of SKA2 on breast cancer, the expression levels of SKA2 in breast cancer tissues and cell lines were evaluated by western blotting, reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining. The results demonstrated that SKA2 expression was increased in breast cancer tissues and cells, and SKA2 overexpression was associated with clinical stage and lymph node metastasis. Functional investigations revealed that SKA2 knockdown in breast cancer cells significantly reduced migration and invasion, and resulted in the decreased expression levels of matrix metalloproteinase (MMP)2 and MMP9. Furthermore, the typical microtubule arrangement was altered in SKA2 small interfering RNA (siSKA2)‑transfected cells. Reduced levels of SKA2 also downregulated the expression of epithelial‑mesenchymal transition proteins, including fibronectin, N‑cadherin and vimentin, whereas there were no alterations in the protein expression levels of E‑cadherin. Conversely, upregulation of SKA2 decreased the expression levels of E‑cadherin, and increased N‑cadherin, fibronectin and vimentin levels. Notably, it was demonstrated that E‑cadherin was translocated from the cytoplasm to the nucleus in siSKA2‑transfected cells. These results demonstrated that SKA2 may be associated with breast cancer metastasis, and siSKA2 inhibited the invasion and metastasis of breast cancer via translocation of E‑cadherin from the cytoplasm to the nucleus.
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Affiliation(s)
- Zhouhui Ren
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China
| | - Tong Yang
- Department of Oncology Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
| | - Pingping Zhang
- Department of Gynaecology, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315012, P.R. China
| | - Kaitai Liu
- Department of Oncology, Ningbo Medical Center, Li Huili Hospital, Ningbo, Zhejiang 315041, P.R. China
| | - Weihong Liu
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China
| | - Ping Wang
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China
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28
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Neely C, You S, Mendoza PM, Aneja R, Sahin AA, Li X. Comparing breast biomarker status between routine immunohistochemistry and FISH studies and Oncotype DX testing, a study of 610 cases. Breast J 2018; 24:889-893. [DOI: 10.1111/tbj.13110] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 11/17/2017] [Accepted: 11/20/2017] [Indexed: 01/23/2023]
Affiliation(s)
- Cameron Neely
- Department of Pathology and Laboratory Medicine; Emory University; Atlanta Georgia
| | - Shuo You
- Winship Cancer Institute, Emory University; Atlanta Georgia
| | - Pia M. Mendoza
- Department of Pathology and Laboratory Medicine; Emory University; Atlanta Georgia
| | - Ritu Aneja
- Department of Biology; Georgia State University; Atlanta Georgia
| | - Aysegul A. Sahin
- Department of Pathology; The University of Texas MD Anderson Cancer Center; Houston Texas
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine; Emory University; Atlanta Georgia
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29
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Voutsadakis IA. Prognostic role of tumor budding in breast cancer. World J Exp Med 2018; 8:12-17. [PMID: 30211020 PMCID: PMC6134264 DOI: 10.5493/wjem.v8.i2.12] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 08/04/2018] [Accepted: 08/13/2018] [Indexed: 02/06/2023] Open
Abstract
Tumor budding, defined as a small number of cancer cells observed in pathology sections detached from the main tumor mass, is a common phenomenon in cancer. It is suggested that cells in buds are in the process of actively moving away from the primary tumor in the first step of metastasis. Tumor budding has been observed in a variety of carcinomas and is best studied in colorectal cancers where it portends poor prognosis. More recently, tumor budding was found to be of prognostic significance in other cancers including breast cancer. Tumor budding in breast cancer is associated with other adverse pathologic factors, such as larger tumor size and lymphovascular invasion, but may have additional independent prognostic value. In the future, standardization of the quantification criteria for tumor budding may further aid in its adoption as a prognostic marker.
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Affiliation(s)
- Ioannis A Voutsadakis
- Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, Ontario, Canada; and Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, P3E 2C6, Canada
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30
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Meisel J, Zhang C, Neely C, Mendoza P, You S, Han T, Liu Y, Sahin AA, O'Regan R, Li X. Evaluation of Prognosis in Hormone Receptor-Positive/HER2-Negative and Lymph Node-Negative Breast Cancer With Low Oncotype DX Recurrence Score. Clin Breast Cancer 2017; 18:347-352. [PMID: 29305309 DOI: 10.1016/j.clbc.2017.12.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 11/13/2017] [Accepted: 12/07/2017] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancers without lymph node metastasis have good prognosis. We compared the prognosis of hormone receptor-positive, HER2-negative, lymph node-negative cancers with Oncotype DX score ranges of 1 to 10 (1-10 group) and 11 to < 18 (11-18 group). PATIENTS AND METHODS A total of 107 cases in the 1-10 group and 225 cases in the 11-18 group were reviewed. All patients received surgery. The use of chemotherapy, radiotherapy, and endocrine therapy, and overall survival (OS), disease-free survival (DFS), and distant metastasis were compared between groups. RESULTS There were no statistical differences in the use of chemotherapy (5.05% vs. 6.05%, P = .724) or radiotherapy (52.53% vs. 59.07%, P = .276) between the 1-10 group and the 11-18 group, respectively. The median OS and DFS were 47 and 45 months, respectively, in the 1-10 group, and 49 and 48 months in the 11-18 group. No significant difference was seen in OS (P = .995), DFS (P = .148), or rates of metastasis (P = .998). The 11-18 group had more death events and distant metastasis (death, 5 events; recurrence, 2 events; metastasis, 2 events) than the 1-10 group (death, 0 events; recurrence, 4 events; metastasis, 0 events). The majority of recurrences seen in both groups were in young patients who failed to comply with their endocrine therapy regimen. CONCLUSION Patients in both the 1-10 group and the 11-18 group had good prognoses. Those who experienced recurrence were more likely to be premenopausal and to have failed to comply with the recommended endocrine therapy regimen. Endocrine therapy remains important in these patients.
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Affiliation(s)
- Jane Meisel
- Department of Hematology and Oncology, Emory University, Atlanta, GA
| | - Chao Zhang
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA
| | - Cameron Neely
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA
| | - Pia Mendoza
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA
| | - Shuo You
- Winship Institute, Emory University, Atlanta, GA
| | - Tatiana Han
- Winship Institute, Emory University, Atlanta, GA
| | - Yuan Liu
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA
| | - Aysegul A Sahin
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ruth O'Regan
- Department of Medicine, University of Wisconsin, Madison, WI
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA.
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31
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Arciero CA, Yang J, Peng L, Ward KC, O'Regan R, Sahin AA, Li X. African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages. Breast Cancer Res Treat 2017; 166:743-755. [PMID: 28856481 DOI: 10.1007/s10549-017-4484-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 08/23/2017] [Indexed: 10/19/2022]
Abstract
PURPOSE Racial disparity of breast cancer in each subtype and substage is not clear. METHODS We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. RESULTS African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2- stages III and IV breast cancer and HR-/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2- stage II cancer and HR-/HER2- stage II cancer. CONCLUSION AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.
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Affiliation(s)
| | - Jing Yang
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Limin Peng
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Kevin C Ward
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Ruth O'Regan
- Department of Medicine, University of Wisconsin, Madison, WI, USA
| | - Aysegul A Sahin
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Suite H175, Atlanta, GA, 30322, USA.
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