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Zhang C, Dong HK, Gao JM, Zeng QQ, Qiu JT, Wang JJ. Advances in the diagnosis and treatment of MET-variant digestive tract tumors. World J Gastrointest Oncol 2024; 16:4338-4353. [PMID: 39554732 PMCID: PMC11551650 DOI: 10.4251/wjgo.v16.i11.4338] [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: 07/08/2024] [Revised: 08/24/2024] [Accepted: 09/10/2024] [Indexed: 10/25/2024] Open
Abstract
The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth, survival, migration and angiogenesis, and its abnormal activation is closely related to the occurrence and development of various tumors. This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors. In terms of diagnosis, the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient, providing a reliable basis for individualized treatment. In terms of treatment, MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials. In addition, the combination of immunotherapy and MET inhibitors also demonstrated potential synergies, further improving the therapeutic effect. However, the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research. In the future, it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients. The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization, and have broad application prospects.
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Affiliation(s)
- Chen Zhang
- The First Department of Radiation Oncology, Lu’an Hospital of Traditional Chinese Medicine of Anhui Province, Lu’an 237000, Anhui Province, China
| | - Hu-Ke Dong
- The Fourth Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Jian-Ming Gao
- The First Department of Oncology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230000, Anhui Province, China
| | - Qi-Qi Zeng
- Department of Gastroenterology, Nanjing University Affiliated Gulou Hospital, Nanjing 210008, Jiangsu Province, China
| | - Jiang-Tao Qiu
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, Beijing 100084, China
| | - Jia-Jia Wang
- Ultrasound of Medicine Department, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Giordano PG, Díaz Zelaya AG, Aguilera Molina YY, Taboada Mostajo NO, Ajete Ramos Y, Ortega García R, Peralta de Michelis E, Meneu Díaz JC. [Clinico-pathological evaluation of tumor budding in the oncological progression of colorectal cancer]. Med Clin (Barc) 2024; 163:159-166. [PMID: 38697893 DOI: 10.1016/j.medcli.2024.02.017] [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: 11/09/2023] [Revised: 02/06/2024] [Accepted: 02/07/2024] [Indexed: 05/05/2024]
Abstract
INTRODUCTION Tumor budding (TB), defined as the presence of individual neoplastic cells or isolated groups of up to 4 cells at the front of tumor invasion, has become an adverse prognostic marker in colorectal cancer (CRC) in recent decades. The prognostic impact of TB in CRC remains not clearly defined and histological methods for its evaluation vary depending on the center. The objective of this study is to investigate the association between TB and CRC, in terms of oncological evolution and pathological stage. METHODS A retrospective observational study was conducted, including patients undergoing curative oncological surgery for CRC between January 2017 and December 2022. The effects of TB on disease-free survival (DFS) and overall survival (OS) were evaluated according to the Kaplan-Meier curves. RESULTS In 78 cases TB was described in the pathology report. TB was present in 56 patients (71.8%), divided into the following categories: low grade in 22 (39.3%), intermediate grade in 17 (30.4%) and high grade in 17 (30.4%). The proportion of patients who presented lymph node metastases, lympho-vascular and perineural invasion was significantly higher in patients with TB (26.8% vs 0%, P=.008; 41.1% vs 4.5%, P=.002; 16.1% vs 0% P=.054; respectively). DFS was 86.3% in low-grade TB, 75.3% in intermediate-grade TB, and 70.3% in high-grade TB. Cases with intermediate and high grade were associated with a shorter OS compared to the low grade group (93.7% and 75.4% vs 100% P=.012, respectively). CONCLUSION These results suggest that TB expression may be a useful risk factor as a prognostic factor for the detection of lymph node metastasis, local recurrence, and distant metastasis in CRC.
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Affiliation(s)
- Pietro Giovanni Giordano
- Servicio de Cirugía General, Visceral y Robótica, Hospital Universitario Ruber Juan Bravo, Madrid, España; Servicio de Patología, Hospital Universitario Ruber Juan Bravo, Madrid, España; Departamento de Medicina, Facultad de Ciencias Biomédicas y de la Salud, Universidad Europea de Madrid, Alcobendas, Madrid, España.
| | | | - Yari Yuritzi Aguilera Molina
- Servicio de Cirugía General, Visceral y Robótica, Hospital Universitario Ruber Juan Bravo, Madrid, España; Servicio de Patología, Hospital Universitario Ruber Juan Bravo, Madrid, España; Departamento de Medicina, Facultad de Ciencias Biomédicas y de la Salud, Universidad Europea de Madrid, Alcobendas, Madrid, España
| | | | - Yelene Ajete Ramos
- Servicio de Cirugía General, Visceral y Robótica, Hospital Universitario Ruber Juan Bravo, Madrid, España
| | - Ricardo Ortega García
- Servicio de Cirugía General, Visceral y Robótica, Hospital Universitario Ruber Juan Bravo, Madrid, España
| | | | - Juan Carlos Meneu Díaz
- Servicio de Cirugía General, Visceral y Robótica, Hospital Universitario Ruber Juan Bravo, Madrid, España; Servicio de Patología, Hospital Universitario Ruber Juan Bravo, Madrid, España; Departamento de Medicina, Facultad de Ciencias Biomédicas y de la Salud, Universidad Europea de Madrid, Alcobendas, Madrid, España
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Yao G, Fang Y, Fu Y, Xu J, Song H, Zhu H, Gu M, Ding X. Tumor budding as an indicator for lymph node metastasis and prognosis of early gastric cancer. J Cancer Res Clin Oncol 2022:10.1007/s00432-022-04522-z. [PMID: 36512103 DOI: 10.1007/s00432-022-04522-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Tumor budding, considered as an independent risk factor reflecting prognosis of some malignant tumors, has been recognized as an important clinicopathological indicator of colorectal carcinoma. However, the evaluation of tumor budding and its clinicopathological significance in gastric cancer remain controversial. AIM To investigate the relationship between tumor budding and clinical biological behavior of early gastric cancer (EGC) and assess the predictive value of tumor budding for lymph node metastasis as well as its impact on prognosis of EGC patients. METHODS Tissue specimens of 164 EGC patients who underwent radical gastrectomy between June 2011 and January 2017 from a single center were selected to carry out HE and CK staining respectively, so as to evaluate tumor budding under light microscopy. Clinicopathological data and follow-up results of all EGC patients were collected for statistical analysis among tumor budding, EGC clinicopathological factors and prognosis. RESULTS Of all 164 EGC patients, there were 84 (51.2%) cases with mucosal invasion and 80 (48.8%) cases with submucosal invasion. Meanwhile, 32 cases (19.5%) had lymph node metastasis, 19 (11.6%) had lympho-vascular invasion and 4 (2.4%) had early recurrence. Tumor budding were observed in 90 (54.9%) patients, with low-grade budding 68 (41.5%) cases and high-grade budding 22 (13.4%) cases. Tumor budding was closely correlated with tumor size (c2 = 6.609, P = 0.037), tumor histologic differentiation (c2 = 10.522, P = 0.032), depth of invasion (c2 = 8.787, P = 0.012), lymph node metastasis (c2 = 24.226, P < 0.01), TNM stage (c2 = 24.226, P < 0.01), lympho-vascular invasion (c2 = 8.225, P = 0.016) and early recurrence (c2 = 6.462, P = 0.040). Additionally, tumor budding was correlated with postoperative survival rate as well. Multiple regression analysis revealed that tumor budding was an independent influencing factor of postoperative 3-year survival rate, 5-year survival rate, OS, DFS and DSS (P < 0.05). Furthermore, tumor budding was an independent risk factor of lymph node metastasis of EGC patients, and high-grade budding was a high-risk indicator of lymph node metastasis. CONCLUSION Tumor budding is related to tumor size, tumor histologic differentiation, depth of invasion, lymph node metastasis, lympho-vascular invasion and early recurrence of EGC. Tumor budding, especially high-grade budding can serve as an indicator for predicting lymph node metastasis of EGC, and high-grade budding could be an important parameter for evaluating prognosis of EGC patients.
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Qian L, Zhang J, Lu S, He X, Feng J, Shi J, Liu Y. Potential key roles of tumour budding: a representative malignant pathological feature of non-small cell lung cancer and a sensitive indicator of prognosis. BMJ Open 2022; 12:e054009. [PMID: 35361643 PMCID: PMC8971788 DOI: 10.1136/bmjopen-2021-054009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To investigate the relationship between tumour budding, clinicopathological characteristics of patients and prognosis in non-small cell lung cancer. STUDY DESIGN A retrospective study was used. PARTICIPANTS We selected 532 patients with non-small cell lung cancer from China, including 380 patients with adenocarcinoma and 152 with squamous cell carcinoma. PRIMARY AND SECONDARY OUTCOME MEASURES Tumour budding was visible using H&E staining as well as pancytokeratin staining. The count data and measurement data were compared using the χ2 test and the t-test, respectively. The overall survival rate was the follow-up result. The survival curves were drawn using the Kaplan-Meier method, and the differences between groups were analysed using the log-rank method. The independent prognostic factor of patients with lung cancer was determined using a multivariate Cox proportional hazard model. RESULTS In patients with lung adenocarcinoma, there was a correlation between tumour budding and spread through air spaces (OR 36.698; 95% CI 13.925 to 96.715; p<0.001), and in patients with squamous cell carcinoma, tumour budding state was closely related to the peritumoural space (OR 11.667; 95% CI 4.041 to 33.683; p<0.001). On Cox regression analysis, multivariate analysis showed that tumour budding, pleural and vascular invasion, spread through air spaces, tumour size, lymph node metastasis, and tumour node metastasis stage were independent risk factors of prognosis for patients with non-small cell lung cancer. CONCLUSIONS As an effective and simple pathological diagnostic index, it is necessary to establish an effective grading system in the clinical diagnosis of lung cancer to verify the value of tumour budding as a prognostic indicator. We hope that this analysis of Chinese patients with non-small cell lung cancer can provide useful reference material for the continued study of tumour budding.
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Affiliation(s)
- Li Qian
- Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Jianguo Zhang
- Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Shumin Lu
- Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xin He
- Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Jia Feng
- Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Jiahai Shi
- Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, China
| | - Yifei Liu
- Pathology, Affiliated Hospital of Nantong University, Nantong, China
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Martin B, Schäfer E, Jakubowicz E, Mayr P, Ihringer R, Anthuber M, Schenkirsch G, Schaller T, Märkl B. Interobserver variability in the H&E-based assessment of tumor budding in pT3/4 colon cancer: does it affect the prognostic relevance? Virchows Arch 2018; 473:189-197. [PMID: 29626253 DOI: 10.1007/s00428-018-2341-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 03/06/2018] [Accepted: 03/15/2018] [Indexed: 12/14/2022]
Abstract
Tumor budding is a mostly accepted adverse prognostic factor in colorectal carcinoma. It is on the cusp of a widespread use after agreement was reached recently on uniform assessment criteria. We investigated whether the interobserver variability has a direct influence on the prognostic relevance in pT3/4 colon cancer in the background of different levels of experience of the investigators. In total, six investigators with different levels of experience evaluated tumor budding on H&E slides in 244 cases with primary diagnosed (2002-2011) colon carcinoma (pT3/4, N+/-, M0). High-grade tumor budding/budding grade 3 (defined as majority assessment among the investigators) was significantly associated with an adverse outcome (overall survival p = 0.03, cancer-specific survival p = 0.08) and the occurrence of distant metastasis (p = 0.009). However, a detailed analysis of the rating results of the individual investigators revealed that only ratings of one investigator (advanced resident) were associated with an adverse outcome (p = 0.01 cancer-specific survival, overall survival p = 0.09, distant metastasis p = 0.002). The results of another investigator (consultant) were significantly associated with distant metastasis (p = 0.007). The kappa values among the investigators have a range between 0.077 and 0.357 (median 0.166). Total agreement of all investigators existed in 109 cases (44.7%). Our results demonstrate that the evaluation of tumor budding on H&E slides in pT3/4 colon cancer goes along with a considerable interobserver variability among investigators of different levels of experience. Furthermore, our results reveal that these findings directly influence the prognostic value.
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Affiliation(s)
- Benedikt Martin
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany.
| | - Eva Schäfer
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Elzbieta Jakubowicz
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Patrick Mayr
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Regina Ihringer
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Matthias Anthuber
- Department of Visceral Surgery, Klinikum Augsburg, Augsburg, Germany
| | | | - Tina Schaller
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Bruno Märkl
- Institute of Pathology, Klinikum Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
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Märkl B, Martin B. [Pathology of early stage cancer of the gastrointestinal tract : Definition, principles and diagnosis]. Chirurg 2018; 89:333-338. [PMID: 29464307 DOI: 10.1007/s00104-018-0602-9] [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: 11/26/2022]
Abstract
BACKGROUND Early stage cancers of the gastrointestinal tract are malignant tumors that are eligible for local therapy regimens and show an excellent prognosis. OBJECTIVE This article explains the histopathological aspects of the various diseases that are covered by this topic. METHODS Organ-preserving therapies are discussed according to their locations and under consideration of the current guidelines and the relevant literature. RESULTS The exact histopathological evaluation of early cancers of the gastrointestinal tract is of crucial importance. It is the essential basis for all further therapy decisions. In most cases, an option for a local resection is given. In comparison to partial or complete organ resections, local resection is associated with a significantly decreased morbidity and reduced length of hospital stays; however, it must be ensured that local therapies do not become responsible for increased rates of tumor recurrence and progression. Therefore, an optimal risk estimation based on a sophisticated histopathological classification is mandatory. This includes the evaluation of the infiltration depth, grading, lymphovascular invasion and resection margins. CONCLUSION Molecular analyses have not yet entered clinical practice. The only exceptions are investigations to detect hereditary diseases. The exact histopathological diagnostic of early gastrointestinal cancers is the basis of an effective and organ-preserving therapy.
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Affiliation(s)
- B Märkl
- Institut für Pathologie, Klinikum Augsburg, Stenglinstraße 2, 86157, Augsburg, Deutschland.
| | - B Martin
- Institut für Pathologie, Klinikum Augsburg, Stenglinstraße 2, 86157, Augsburg, Deutschland
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Tumor Budding, uPA, and PAI-1 in Colorectal Cancer: Update of a Prospective Study. Gastroenterol Res Pract 2017; 2017:6504960. [PMID: 28286517 PMCID: PMC5327786 DOI: 10.1155/2017/6504960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 12/18/2016] [Accepted: 01/05/2017] [Indexed: 12/20/2022] Open
Abstract
Aims. The prognostic role of the proteases uPA and PAI-1, as well as tumor budding, in colon cancer, has been investigated previously. Methods. We provide 6-year follow-up data and results of the validation set. The initial test set and validation set consisted of 55 colon cancers and 68 colorectal cancers, respectively. Tissue samples were analyzed for uPA and PAI-1 using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Tumor budding was analyzed on cytokeratin-stained slides. Survival analyses were performed using cut-offs that were determined previously. Results. uPA was not prognostic for outcome. PAI-1 showed a trend towards reduced cancer specific survival in PAI-1 high-grade cases (68 versus 83 months; P = 0.091). The combination of high-grade PAI-1 and tumor budding was associated with significantly reduced cancer specific survival (60 versus 83 months; P = 0.021). After pooling the data from both sets, multivariate analyses revealed that the factors pN-stage, V-stage, and a combination of tumor budding and PAI-1 were independently prognostic for the association with distant metastases. Conclusions. A synergistic adverse effect of PAI-1 and tumor budding in uni- and multivariable analyses was found. PAI-1 could serve as a target for anticancer therapy.
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Märkl B, Wilhelms N, Anthuber M, Schenkirsch G, Schlimok G, Oruzio D. Circulating cytokeratin-positive cells and tumor budding in colorectal cancer. World J Clin Oncol 2016; 7:433-440. [PMID: 28008384 PMCID: PMC5143437 DOI: 10.5306/wjco.v7.i6.433] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Revised: 09/10/2016] [Accepted: 10/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether circulating cytokeratin-positive (CK+) cells in the mesenteric blood of resected colorectal specimens are prognostic and correlate with tumor budding.
METHODS Fifty-six colorectal specimens were collected between 9/2007 and 7/2008. Blood from the mesenteric vein was drawn immediately after receiving the fresh and unfixed specimens in the pathology department. After separation of the mononuclear cells by Ficoll-Hypaque density-gradient centrifugation, cytological smears were immunocytochemically stained for CK18. Tumor budding was evaluated on slides stained for pan-cytokeratin. The identification of ≥ 30 buds/1.3 mm2 was defined as high grade budding.
RESULTS CK+ cells and clusters were identified in 29 (48%) and 14 (25%) of the samples, respectively. Two cells were identified in one of three non-malignant cases. Clusters were found exclusively in malignant cases. The occurrence of CK+ cells or clusters was not associated with any of the evaluated clinicopathological factors, including surgical technique and tumor budding. Moreover, the occurrence of CK+ cells or clusters had no influence on the cancer-specific survival [75 mo (CI: 61; 88) vs 83 mo (CI: 72; 95) and 80 mo (CI: 63; 98) vs 79 mo (CI: 69; 89), respectively].
CONCLUSION CK+ cells and showed neither prognostic significance nor an association with tumor budding. It is very likely that CK18-staining is not specific enough to identify the relevant cells.
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Märkl B, Märkl M, Schaller T, Mayr P, Schenkirsch G, Kriening B, Anthuber M. A new simple morphology-based risk score is prognostic in stage I/II colon cancers. Cancer Med 2016; 5:1492-501. [PMID: 27167601 PMCID: PMC4867555 DOI: 10.1002/cam4.737] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 03/21/2016] [Accepted: 03/23/2016] [Indexed: 12/27/2022] Open
Abstract
A portion of stage I/II colon cancers (10-20%) exhibit an adverse clinical course. The administration of adjuvant chemotherapy is recommended only in certain high-risk situations. However, these risk factors recently failed to predict benefit from adjuvant therapy. We composed a new morphology-based risk score that includes pT1/2 versus 3/4 stage, vascular or lymphovascular invasion, invasion type according to Jass, tumor budding and paucity (less than two) of lymph nodes larger than 5 mm. The occurrence of each of these factors accounts for one point in the score (Range 0-5). This score was evaluated in a retrospective study that included 301 cases. The overall survival differed significantly between the three groups with median survival times of 103, 90, and 48 months, respectively. Multivariable analysis revealed morphology-based risk-high risk and low risk-as the sole independent factors for the prediction of death. Morphology-based risk scoring was superior to microsatellite status and NCCN risk stratification. This method identifies a group of patients that comprises 18% of the stage II cases with an adverse clinical course. Further studies are necessary to confirm its prognostic value and the possible therapeutic consequences.
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Affiliation(s)
- Bruno Märkl
- Institute of Pathology, Klinikum Augsburg, Augsburg, Germany
| | | | - Tina Schaller
- Institute of Pathology, Klinikum Augsburg, Augsburg, Germany
| | - Patrick Mayr
- Institute of Pathology, Klinikum Augsburg, Augsburg, Germany
| | - Gerhard Schenkirsch
- Clinical and Population-Based Cancer Registry Augsburg, Klinikum Augsburg, Augsburg, Germany
| | - Bernadette Kriening
- Department of Visceral- and Transplantation Surgery, Klinikum Augsburg, Augsburg, Germany
| | - Matthias Anthuber
- Department of Visceral- and Transplantation Surgery, Klinikum Augsburg, Augsburg, Germany
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van Wyk H, Park J, Roxburgh C, Horgan P, Foulis A, McMillan DC. The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: A systematic review. Cancer Treat Rev 2015; 41:151-9. [DOI: 10.1016/j.ctrv.2014.12.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Revised: 12/11/2014] [Accepted: 12/12/2014] [Indexed: 02/07/2023]
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Niwa Y, Yamada S, Koike M, Kanda M, Fujii T, Nakayama G, Sugimoto H, Nomoto S, Fujiwara M, Kodera Y. Epithelial to mesenchymal transition correlates with tumor budding and predicts prognosis in esophageal squamous cell carcinoma. J Surg Oncol 2014; 110:764-9. [PMID: 24975035 DOI: 10.1002/jso.23694] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 05/14/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Epithelial to mesenchymal transition (EMT) is considered to play an important role in cancer invasion. Tumor budding is a prognostic factor in esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore the correlation between EMT and tumor budding. METHODS Surgical specimens from 78 cases of ESCC resected without preoperative treatment between 2001 and 2013 were enrolled in the study. The mRNA expressions of E-cadherin and vimentin were measured in cancerous tissues using real-time PCR, and each tumor was classified into either epithelial or mesenchymal group. Tumor budding was evaluated in H&E-stained slides and divided into two groups; low-grade budding (<3) and high-grade budding (≥3). RESULTS The 5-year survival rate in the epithelial group was significantly higher than that in the mesenchymal group (62.0% vs. 31.5%, P = 0.021). Survival rate of patients in the low-grade budding group was significantly higher than that of patients in the high-grade budding group (75.1% vs. 25.9%, P < 0.001). High-grade tumor budding was significantly associated with the mesenchymal group (P = 0.009). CONCLUSION EMT was found to occur in ESCC and was significantly associated with tumor budding. Tumor budding was identified as a significant independent prognostic factor among the current population of ESCC.
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Affiliation(s)
- Yukiko Niwa
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Liang F, Cao W, Wang Y, Li L, Zhang G, Wang Z. The prognostic value of tumor budding in invasive breast cancer. Pathol Res Pract 2013; 209:269-75. [PMID: 23561623 DOI: 10.1016/j.prp.2013.01.009] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 12/27/2012] [Accepted: 01/27/2013] [Indexed: 12/11/2022]
Abstract
We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.
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Affiliation(s)
- Fenli Liang
- Center for Cancer Research, First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, China
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