Abstract 1737: Co-existence of positive MET FISH status with EGFR mutations signifies poor prognosis in lung adenocarcinoma

Abstract

Abstract MET, which is located in 7q31, is a receptor tyrosine kinase for hepatocyte growth factor. Overexpression of MET has been reported in various malignancies and is associated with cell proliferation, inhibition of apoptosis, and metastasis. MET amplification has been reported to contribute to acquired resistance to epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer(NSCLC), being observed among 5-10% of those patients. Therefore, MET gene alterations could be both prognostic and predictive. To evaluate MET gene copy number, fluorescence in situ hybridization (FISH), real-time PCR, and comparative genomic hybridization (CGH) have been used. The results of real-time PCR do not directly reflect cancer cells. CGH is not suitable for the evaluation of a large number of specimens due to cost. Therefore, FISH is the most practical method for evaluation of MET gene copy number. However, the frequency of positive cases varies due to a lack of standardized criteria. We evaluated MET gene copy number in lung adenocarcinoma and its association with clinicopathological characteristics. FISH was applied to evaluate high MET gene copy number and true amplification in 138 lung adenocarcinoma patients using two criteria: the Cappuzzo scoring system and PathVysion. MET positive cases according to the Cappuzzo scoring system evidenced both aneuploidy and true amplification, whereas PathVysion revealed only amplification. Proportion of MET FISH positive cases was 15% and 4% determined by the Cappuzzo system and PathVysion, respectively. PathVysion demonstrated higher frequencies of MET FISH positives among men and smokers and evidenced no MET FISH positives in patients with bronchioloalveolar carcinoma, which is recognized as pure lepidic growth without invasion of stroma, blood vessels, or pleura. Prognosis was significantly associated with MET FISH positive only as defined by the PathVysion system (gene amplification), not by the Cappuzzo system. However, progression-free survival time of patients with both EGFR mutations and MET FISH positive defined by the Cappuzzo scoring system was significantly shorter than with EGFR mutations alone. These results suggest that MET FISH is a potential prognostic factor and co-existence of EGFR mutation and MET FISH positive status evidences poorer prognosis compared to EGFR mutation alone, which is consistent with the results of in vitro experiments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1737. doi:1538-7445.AM2012-1737