Correlation between expression of C-met and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in lung adenocarcinoma

Objective To detect C-met protein expression and gene amplification in lung adenocarcinoma, and to analyze their relationship with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance and prognosis. Methods A total of 120 cases of lung adenocarcinoma diagnosed in Shanxi Provincial Cancer Hospital from January 2011 to May 2013 were selected. The expressions of C-met protein and C-met gene amplification were conducted by immunohistochemistry (IHC) method and fluorescence in situ hybridization (FISH), and all patients were followed up. The relationship between the expression of C-met protein and gene amplification with clinicopathological features and EGFR-TKI resistance and prognosis were analyzed. Results The high expression of C-met protein and gene amplification in 120 tissues were 17.5 % (21/120), 10.83 % (13/120). Of the 80 patients treated with EGFR-TKI, the incidence of C-met protein high expression was 30.43 % (14/46) in patients with drug resistance, which was significantly higher than that in patients without drug resistance (11.76 %, 4/34), the difference was statistically significant (χ2 = 3.908, P= 0.048). The rate of C-met gene amplification was 19.57 % (9/46) in patients with drug resistance, which was significantly higher than that in patients without drug resistance (2.94%, 1/34) the difference was statistically significant (P= 0.038). The expression of C-met protein in 46 patients with drug resistance was positively correlated with gene amplification (r= 0.388, P= 0.008), but in 40 patients without TKI, the expression of C-met protein was not correlated with gene amplification (r= 0.279, P= 0.081). The high expression of C-met protein was correlated with age, pathological grade and clinical stage (all P < 0.05), while C-met gene amplification was related to clinical stage (P= 0.036). Cox regression analysis suggested that C-met gene amplification was an independent prognostic factor (P= 0.034). Conclusions C-met protein expression and gene amplification are risk factors for EGFR-TKI resistance. C-met gene amplification suggests poor prognosis, and can be used as an independent factor for prognostic evaluation. Key words: Lung neoplasms; Proto-oncogene proteins c-met; Receptor, epidermal growth factor; Tyrosine kinase inhibitor; Prognosis; Drug resistance, neoplasm