C-MET/Phospho-MET Protein Expression and MET Gene Copy Number in Non-small Cell Lung Carcinomas

Abstract

The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. The aim of this study was to examine the correlations between c-MET/phospho-MET expression as well as MET gene copy number alterations and overall survival (OS) in non-small cell lung carcinomas (NSCLCs). We analyzed 906 NSCLCs including 704 adenocarcinomas (ADCs), 150 squamous cell carcinomas (SCCs), 43 sarcomatoid carcinomas, and 9 large cell carcinomas. The mutational status of epidermal growth factor receptor and K-ras and anaplastic lymphoma kinase rearrangements were retrospectively examined. We performed immunohistochemistry to detect c-MET/phospho-MET expression and MET gene copy number using bright-field in situ hybridization (BISH). c-MET/phospho-MET expression and MET BISH positivity were observed in 22.2%, 5.6%, and 10.9% of NSCLCs, respectively; they were more prevalent in ADCs (27.3%, 6.9%, and 11.5%, respectively) and sarcomatoid carcinomas (20.9%, 9.3%, and 36.6%, respectively) than in SCCs and large cell carcinomas. Among ADCs, poorly differentiated cases exhibited c-MET expression and MET BISH positivity more commonly than well-differentiated ones. An analysis of all patients revealed that c-MET/phospho-MET expression and MET BISH positivity were not correlated with OS. However, when SCC cases were excluded, both univariate (p=0.019) and multivariate (p=0.020) analyses revealed a significant correlation between MET BISH positivity and OS. c-MET/phospho-MET expression and MET BISH positivity differed according to histological type. Among ADCs, c-MET expression and MET BISH positivity were more common in poorly differentiated cases. MET BISH positivity was an independent prognostic factor in nonsquamous NSCLCs.