MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma

MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry was used for MET protein expression analysis, and fluorescence in situ hybridization was used for MET amplification detection. Both analyses were performed in tissue microarrays containing 294 colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. Polymerase chain reaction sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival and disease-free survival. Multivariate analysis revealed that positive MET protein expression was an independent risk factor for disease-free survival but not for overall survival. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and exon 14 mutation are extremely rare events in colorectal adenocarcinoma.