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Original Articles
- Gastrointestinal cancer
- Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers
- Hyun Gu Lee, Yeseul Kim, Mi-Ju Kim, Yeon Wook Kim, Sun-Young Jun, Deokhoon Kim, In Ja Park, Seung-Mo Hong
- Cancer Res Treat. 2026;58(1):264-274. Published online February 18, 2025
- DOI: https://doi.org/10.4143/crt.2024.947
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Abstract
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Supplementary Material
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ePub - Purpose
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
Materials and Methods
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor.
Results
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
Conclusion
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.
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- Stage Evaluation of Cystic Duct Cancer
- Yeseul Kim, You-Na Sung, Haesung Jung, Kyung Jin Lee, Daegwang Yoo, Sun-Young Jun, HyungJun Cho, Shin Hwang, Woohyung Lee, Seung-Mo Hong
- Cancer Res Treat. 2025;57(2):528-538. Published online September 19, 2024
- DOI: https://doi.org/10.4143/crt.2024.660
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Cystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs.
Materials and Methods
T category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata’s classifications (type 1, confined within cystic duct [CD]; combined types 2-4, extension beyond CD) and compared them.
Results
No significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1-T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1-T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types.
Conclusion
Unlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.
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- 109 Download
- 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
PDFSupplementary MaterialPubReaderePub
- 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 in Cancer and MET-Targeted Therapy: Detection Strategies, Treatment Efficacy, and Emerging Technologies
Jieun Park, Chaithanya Chelakkot, Ji-Hye Nam, Hun Seok Lee, Chae Rin Kim, Yeonwoo Lee, Mi-Sook Lee, Yoon-La Choi, Young Kee Shin
Targeted Oncology.2025; 20(5): 767. 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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- 230 Download
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