Interim analysis of CALGB 150607: A pilot project to study the expression of MET and P53 in resected lung adenocarcinoma specimens.

10633 Background: MET is a receptor tyrosine kinase that has been shown to be dysregulated in a number of malignancies, including non-small cell lung cancer (NSCLC). In patients with NSCLC, alterations in MET, and its ligand, HGF, have been associated with higher pathological stage and worse outcome in a number of smaller studies. The primary objective of this study is to determine the correlation between MET expression with stage and overall survival in adenocarcinoma (AC) patients in a large series of patients. The secondary objectives are 1) to determine the correlation with MET mutations, epithelial mesenchymal transition (EMT), EGFR mutations and expression, KRAS mutations, and P53 mutations and expression with respect to survival; and 2) to determine the impact of MET amplification on prognosis. Methods: MET, EGFR exons 18-21, P53 exons 4-10, and KRAS exon 2 were sequenced using standard PCR and sequencing techniques. Standard immunohistochemistry (IHC) techniques were used to evaluate total MET, phosphorhylated (p)MET (Y1003 and Y1230/34/35), P53, HGF, EGFR and E-cadherin expression. Quantitative PCR was used to determine MET gene copy number. A total of 280 patients will be included in this study, and an interim analysis will be presented here. Results: Immunohistochemical data is available for 20 patients. High expression of total MET was seen in 95% of patients, high Y1003 MET expression was seen in 80% of patients, high Y1230/34/35 MET expression was seen in 55% of patients. Six out of 40 patients have been found to carry a mutation in the MET gene; three of these represent novel mutations in the semaphorin and juxtamembrane domains that have not been previously reported in the literature. MET amplification data will be forthcoming. Conclusions: Both MET and pMET are highly expressed in resected lung adenocarcinoma specimens. Novel MET mutations have been identified in key domains. Updated results and correlation with overall survival will be presented. No significant financial relationships to disclose.