MET overexpression and gene amplification: prevalence, clinico-pathological characteristics and prognostic significance in a large cohort of patients with surgically resected NSCLC.

Abstract

The prevalence of overexpression and amplification of the proto-oncogene mesenchymal epithelial transition (MET) in non-small cell lung cancer (NSCLC) varies greatly in the literature. Since MET is a potential treatment target, knowledge of its prevalence and prognostic importance is crucial. We investigated MET expression and gene status in 735 NSCLC cases using tissue microarrays. Prognostic significance as well as correlations with various clinico-pathological parameters were evaluated. The prevalence of MET overexpression was 17% and MET amplification was present in 2.4% of cases. MET overexpression was found more frequently in adenocarcinomas (and TTF1-positive tumors) and female patients and was also associated with expression of members of the epidermal growth factor receptor (EGFR) signaling cascade. MET amplified tumors tended to express MET more frequently and more intensively. MET expression or gene status did not prove to be relevant prognostic factors. MET may not be an unequivocal prognostic parameter; however, its expression is associated with certain clinico-pathological characteristics and with EGFR and downstream EGFR effectors. This could be an important point for future studies addressing targeted MET therapy and should be considered as a possible means of optimizing the benefit and minimizing undesirable effects.