Evaluation of c-MET Aberrations in Colorectal Cancer Based on Dual IHC/FISH Detection Strategy: New Evidence for Targeted Therapy Screening
10.3971/j.issn.1000-8578.2026.26.0070
- VernacularTitle:基于IHC与FISH双检策略的结直肠癌c-MET异常评估：靶向治疗筛选的新依据
- Author:
Yanan YANG
1
;
Yanggeling ZHANG
1
;
De WU
1
;
Luyao ZHANG
1
;
Huiting HUANG
1
;
Junqiu YUE
1
;
Shiwei XIAO
1
Author Information
1. Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, China;Hubei Provincial Clinical Research Center for Colorectal Cancer, Wuhan 430079, China;Wuhan Clinical Research Center for Colorectal Cancer, Wuhan 430079, China.
- Publication Type:CLINICALRESEARCH
- Keywords:
Colorectal cancer;
c-MET protein;
MET gene amplification;
Clinicopathologic characteristics;
KRAS mutant
- From:
Cancer Research on Prevention and Treatment
2026;53(8):589-599
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression characteristics of c-MET protein in colorectal cancer (CRC) and its associations with clinicopathological parameters, MET gene amplification status, and prognosis, and to evaluate the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) detection strategies, thereby providing evidence for patient selection for MET-targeted therapy. Methods A total of 193 formalin-fixed paraffin-embedded (FFPE) tissue samples from CRC patients were collected. Immunohistochemistry (IHC) was used to detect c-MET protein expression, and fluorescence in situ hybridization (FISH) was performed to evaluate MET gene amplification status. The associations between c-MET protein expression and clinicopathological characteristics, including KRAS, NRAS, and BRAF mutation status, as well as progression-free survival (PFS), were analyzed. The concordance between IHC and FISH detection results was also evaluated. Results c-MET protein expression was significantly higher in tumor tissues than in adjacent normal tissues (P<0.05). Significant differences in c-MET expression were observed between primary tumors and liver or peritoneal/pelvic metastatic lesions (P<0.05). The proportion of high c-MET expression was significantly higher in KRAS-mutant patients than in KRAS wild-type patients (41.38% vs. 16.92%, P<0.05). The MET gene amplification rate was 8.29% (16/193), including clustered or diffuse amplification in 1.55% (3/193) and heterogeneous amplification in 6.74% (13/193). No MET exon 14 skipping mutation or amplification was detected by next-generation sequencing (NGS). Using an IHC H-Score≥150 as the threshold, the positive percent agreement (PPA) between IHC-detected c-MET protein expression and FISH-detected MET gene amplification was 100%. All clustered MET amplification regions exhibited diffuse strong c-MET expression (IHC 3+). No statistically significant association was observed between c-MET expression level and PFS (P>0.05). Conclusion High c-MET expression may represent a potential therapeutic target for KRAS-mutant CRC patients. An H-Score ≥150 is recommended as the initial screening threshold to rapidly identify patients suitable for MET-targeted therapy, with FISH testing when necessary. Diffuse strong c-MET expression (IHC 3+) shows high concordance with clustered MET gene amplification.
