Correlation among Genetic Variations of c-MET in Chinese Patient with Non-Small Cell Lung Cancer

Abstract

Aims: The aim of this study was to determine the relationship between amplification, protein expression and somatic mutation of c-MET in advanced Non-small cell lung cancer. The influence of c-MET abnormalities on clinical outcomes of patients undergoing Crizotinib therapy for treatment of Non-Small Cell Lung Cancer was also evaluated. Methods: c-MET protein expression, gene copy number (GCN) and somatic mutation for exon 14 were detected by Immunohistochemistry, fluorescent In Situ Hybridization and Denaturing High Performance Liquid Chromatography, respectively, in a large series of 196 NSCLC patients. The correlation of c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar’s test. Results: c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) was shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. All cases that were c-MET FISH positive were also shown to express c-MET by IHC. However, only half of the cases that were positive for c- MET expression were found to be FISH positive. Among 31 patients with moderate c-MET IHC staining, 11 cases (35.5%) were FISH positive, while 16/25 cases with high IHC staining were also FISH positive. Six patients received Crizotinib as a first-line or second/third-line therapy. Among them, three cases showed ALK protein expression, two patients showed expression of the ROS1 fusion gene, and one was positive for c-MET expression by IHC. The response to Crizotinib in the three patients positive for ALK were all PR, while the c-MET positive patient showed SD and both cases with expression of the ROS1 gene showed PD. Conclusions: IHC could be a preliminary screening test to facilitate selection of patients with c-MET amplification for ALK inhibitor therapy.