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Original Articles
- Prevalence and Clinicopathological Significance of MET Overexpression and Gene Amplification in Patients with Gallbladder Carcinoma
- Yeseul Kim, Seong Sik Bang, Seungyun Jee, Sungeon Park, Su-Jin Shin, Kiseok Jang
- Cancer Res Treat. 2020;52(2):481-491. Published online October 24, 2019
- DOI: https://doi.org/10.4143/crt.2019.370
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Abstract
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Supplementary Material
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ePub - Purpose
Mesenchymal epithelial transition (MET) is a proto-oncogene that encodes a heterodimeric transmembrane receptor tyrosine kinase for the hepatocyte growth factor. Aberrant MET signaling has been described in several solid tumors—especially non-small cell lung cancer— and is associated with tumor progression and adverse prognosis. As MET is a potential therapeutic target, information regarding its prevalence and clinicopathological relevance is crucial.
Materials and Methods
We investigated MET expression and gene amplification in 113 gallbladder cancers using tissue microarray. Immunohistochemistry was used to evaluate MET overexpression, and silver/fluorescence in situ hybridization (ISH) was used to assess gene copy number.
Results
MET overexpression was found in 37 cases of gallbladder carcinoma (39.8%), and gene amplification was present in 17 cases (18.3%). MET protein expression did not correlate with MET amplification. MET amplification was significantly associated with aggressive clinicopathological features, including high histological grade, advanced pT category, lymph node metastasis, and advanced American Joint Committee on Cancer stage. There was no significant correlation between any clinicopathological factors and MET overexpression. No difference in survival was found with respect to MET overexpression and amplification status.
Conclusion
Our data suggested that MET might be a potential therapeutic target for targeted therapy in gallbladder cancer, because MET amplification was found in a subset of tumors associated with adverse prognostic factors. Detection of MET amplification by ISH might be a useful predictive biomarker test for anti-MET therapy. -
Citations
Citations to this article as recorded by
- Genomic and molecular landscape of gallbladder cancer elucidating pathogenic mechanisms novel therapeutic targets and clinical implications
Manishankar Kumar, Arun Kumar, Abhinav Srivastav, Ashok Ghosh, Dhruv Kumar
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis.2025; 830: 111896. CrossRef - Structure based multi-targeted screening, docking, DFT and simulation of anticancer natural compounds against gallbladder cancer
Suchitra Singh, Janhavi Yadav, Surbhi Singh, Sumanta Kumar Sahu, Puneet Puneet, Royana Singh
In Silico Pharmacology.2025;[Epub] CrossRef - MET alterations detection platforms and clinical implications in solid tumors: a comprehensive review of literature
Pei Yuan, Xuemin Xue, Tian Qiu, Jianming Ying
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef - EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance
Yeseul Kim, Seungyun Jee, Hyunsung Kim, Seung Sam Paik, Dongho Choi, Su Hyun Yoo, Su-Jin Shin
The Oncologist.2024; 29(8): e1051. CrossRef - Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer
Qiu-Xiao Yu, Ping-Ying Fu, Chi Zhang, Li Li, Wen-Ting Huang
World Journal of Gastrointestinal Surgery.2024; 16(5): 1395. CrossRef - Which therapy in biliary tract cancer? Review of main concerns in diagnosis and choice of therapy in advanced setting, current standard, and new options
Ester Oneda, Serena Astore, Laura Gandolfi, Laura Melocchi, Alberto Zaniboni
Expert Opinion on Pharmacotherapy.2024; 25(13): 1807. CrossRef - Acquired MET amplification in non-small cell lung cancer is highly associated with the exposure of EGFR inhibitors and may not affect patients' outcome
Wei Yin, Wei Liu, Ming Guo, Zhenya Tang, Gokce Toruner, Melissa Robinson, Joanne Cheng, Shimin Hu, L. Jeffrey Medeiros, Guilin Tang
Experimental and Molecular Pathology.2021; 118: 104572. CrossRef - Novel biomarkers for the diagnosis and prognosis of gallbladder cancer
Hong Ze Lin, Tao Zhang, Ming Yu Chen, Ji Liang Shen
Journal of Digestive Diseases.2021; 22(2): 62. CrossRef - A case report of response to crizotinib in chemotherapy-refractory metastatic gallbladder cancer with met amplification and acquired resistance resulting from the loss of MET amplification
Hongna Sun, Xiaofen Li, Shuang Dai, Xudong Shen, Meng Qiu
Precision Clinical Medicine.2021; 4(3): 209. CrossRef - Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer
Matteo Canale, Manlio Monti, Ilario Giovanni Rapposelli, Paola Ulivi, Francesco Giulio Sullo, Giulia Bartolini, Elisa Tiberi, Giovanni Luca Frassineti
Cancers.2021; 13(22): 5671. CrossRef - Testing for ROS1, ALK, MET, and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcinomas
Jeremy Augustin, Caroline Gabignon, Aurélie Scriva, Laëtitia Menu, Claire Calmel, Olivier Scatton, François Paye, Jean-François Fléjou, Françoise Praz, Pascale Cervera, Dominique Wendum
Virchows Archiv.2020; 477(1): 33. CrossRef - Targeted-gene sequencing of an undifferentiated gallbladder carcinoma: a case report
Ying Xiao, Canhong Xiang, Di Yang, Benqi Zhao, Yong Li, Hongfang Yin
Diagnostic Pathology.2020;[Epub] CrossRef - Overview of current targeted therapy in gallbladder cancer
Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef
- Genomic and molecular landscape of gallbladder cancer elucidating pathogenic mechanisms novel therapeutic targets and clinical implications
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- Growth Suppression and Induction of Chemosensitivity in Human Gallbladder Epithelial Carcinoma Cells (GBCE) by Adenovirus-Mediated Transfer of the Wild-type p53 Gene
- Sung Bae Kim, Myung Hwan Kim, Sung Koo Lee, Tae Won Kim, Cheolwon Suh, Jeong Sik Shin, Jung Sun Park, Eun Soon Kim, Gyungyub Gong, Jung Shin Lee, Woo Kun Kim, Sang Hee Kim
- Cancer Res Treat. 2003;35(6):521-527. Published online December 31, 2003
- DOI: https://doi.org/10.4143/crt.2003.35.6.521
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Abstract
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- PURPOSE
Mutations in the p53 gene are reported in 50~90% of gallbladder and bile duct cancer, and have been implicated in chemoresistance. We undertook this study to determine whether the introduction of the wild type p53 gene into GBCE (human gallbladder cancer cell line with a heterozygous p53 mutation) by an adenoviral vector could increase the sensitivity of the cell to 5-FU, a commonly used drug in the treatment of gallbladder cancer. MATERIALS AND METHODS: GBCE cells were transfected with either Ad/p53 or Ad/E1 in the presence of 5-FU. Gene expression was confirmed by western blotting. Nude mice were injected subcutaneously with GBCE cells. When tumors formed, intratumoral injection of Ad/p53 was performed. Reduction of tumor size was compared in two weeks of Ad/p53 gene transfection. RESULTS: Ad/53 transfection induced a dose-dependent inhibition of tumor growth. Tumor colony formation was more inhibited with p53 gene transfection than with mock transfection in the presence of 5-FU. The reduction in tumor size was more pronounced with p53 transfection than with mock infection.
CONCLUSION
These treatment modalities could be utilized in the treatment of p53 mutant human gallbladder cancers.
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- 17 Download
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