Prevalence and Clinicopathological Significance of METOverexpression and Gene Amplification in Patients withGallbladder Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

ABSTRACT

Purpose@#Mesenchymal epithelial transition (MET) is a proto-oncogene that encodes a heterodimerictransmembrane receptor tyrosine kinase for the hepatocyte growth factor. Aberrant METsignaling 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 potentialtherapeutic target, information regarding its prevalence and clinicopathological relevanceis crucial. @*Materials and Methods@#We investigated MET expression and gene amplification in 113 gallbladder cancers usingtissue microarray. Immunohistochemistry was used to evaluate MET overexpression, andsilver/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 geneamplification was present in 17 cases (18.3%). MET protein expression did not correlatewith MET amplification. MET amplification was significantly associated with aggressive clinicopathologicalfeatures, including high histological grade, advanced pT category, lymphnode metastasis, and advanced American Joint Committee on Cancer stage. There was nosignificant correlation between any clinicopathological factors and MET overexpression. Nodifference 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 therapyin gallbladder cancer, because MET amplification was found in a subset of tumors associatedwith adverse prognostic factors. Detection of MET amplification by ISH might be a usefulpredictive biomarker test for anti-MET therapy.