Yu QX, Fu PY, Zhang C, Li L, Huang WT. Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer. World J Gastrointest Surg 2024; 16(5): 1395-1406 [PMID: 38817281 DOI: 10.4240/wjgs.v16.i5.1395]
Corresponding Author of This Article
Wen-Ting Huang, MD, Chief, Chief Doctor, Professor, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 113 Baohe Avenue, Longgang District, Shenzhen 518116, Guangdong Province, China. huangwt@cicams.ac.cn
Research Domain of This Article
Pathology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Surg. May 27, 2024; 16(5): 1395-1406 Published online May 27, 2024. doi: 10.4240/wjgs.v16.i5.1395
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
Qiu-Xiao Yu, Ping-Ying Fu, Chi Zhang, Li Li, Wen-Ting Huang, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
Author contributions: Yu QX and Li L designed the research study; Yu QX performed the research; Fu PY and Zhang C contributed new reagents and analytic tools; Yu QX analyzed the data; Yu QX and Huang WT wrote the manuscript; and all authors have read and approve the final manuscript.
Supported bythe National Natural Science Foundation of China, No. 82002829.
Institutional review board statement: The study was reviewed and approved by the ethics committee of Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences (Approval No. KYLX2023-107).
Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wen-Ting Huang, MD, Chief, Chief Doctor, Professor, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 113 Baohe Avenue, Longgang District, Shenzhen 518116, Guangdong Province, China. huangwt@cicams.ac.cn
Received: January 10, 2024 Revised: February 22, 2024 Accepted: April 11, 2024 Published online: May 27, 2024 Processing time: 134 Days and 9.1 Hours
Abstract
BACKGROUND
Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related mortality worldwide. Mesenchymal-epithelial transition factor (MET) gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment. MET amplification has been reported in CRC, but data are very limited. Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice.
AIM
To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy.
METHODS
A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited. All patients were without RAS/RAF mutation or microsatellite instability-high. MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Correlations between MET aberration and pathological features were detected using the chi-squared test. Progression free survival (PFS) during the two-year follow-up was detected using the Kaplan-Meier method and log rank test. The results of MET FISH and IHC were compared using one-way ANOVA.
RESULTS
Polysomy-induced MET amplification was observed in 14.4% of cases, and focal MET amplification was not detected. Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis (LNM) (P < 0.001) and higher tumor budding grade (P = 0.02). In the survival analysis, significant difference was detected between patients with amplified- and non-amplified MET in a two-year follow-up after the first diagnosis (P = 0.001). C-MET scores of 0, 1+, 2+, and 3+ were observed in 1.4%, 24.9%, 54.7%, and 19.0% of tumors, respectively. C-MET overexpression correlated with higher frequency of LNM (P = 0.002), but no significant difference of PFS was detected between patients with different protein levels. In terms of concordance between MET FISH and IHC results, MET copy number showed no difference in c-MET IHC 0/1+ (3.35 ± 0.18), 2+ (3.29 ± 0.11) and 3+ (3.58 ± 0.22) cohorts, and the MET-to-CEP7 ratio showed no difference in three groups (1.09 ± 0.02, 1.10 ± 0.01, and 1.09 ± 0.03).
CONCLUSION
In CRC, focal MET amplification was a rare event. Polysomy-induced MET amplification correlated with adverse pathological characteristics and poor prognosis. IHC was a poor screening tool for MET amplification.
Core Tip: This study aimed to investigate pathological significance of mesenchymal-epithelial transition factor (MET) amplification in therapy-naïve colorectal cancer (CRC) and to propose a feasible screening strategy in clinical practice. In CRC harboring no RAS/RAF mutation or microsatellite instability, focal MET amplification was a rare event, while polysomy-caused MET amplification was observed in 14.4% of patients. Polysomy-caused MET amplification significantly correlated with frequent lymph node metastasis and higher tumor budding grade, which were two independent predictors of unfavorable CRC survival. Consistently, we discovered that MET amplification predicted poor outcome in a two-year follow-up. To our knowledge, this study firstly proved that c-MET immunohistochemistry (IHC) was not a suitable screening tool for MET amplification in CRC, and we recommend that tissue should be prioritized for fluorescence in situ hybridization over IHC to determine MET amplification.
