Association of epithelial to mesenchymal transition with efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild type.

Abstract

7535 Background: The epithelial to mesenchymal transition (EMT) is a fundamental biological process during which epithelial cells change to a mesenchymal phenotype, it has a profound impact on cancer progression and treatment. The purpose of this study was to investigate the role of EMT to predict the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) patients. Methods: We evaluated the correlation between EMT and sensitivity to EGFR-TKIs in advanced NSCLC patients. Immunohistochemistry was used to examine the expression of EMT markers, E-cadherin, fibronectin, N-cadherin and vimentin and ARMs was used to detect the EGFR mutation in tumor specimens obtained before the treatment. The EMT phenotype status was determined according to the expression of E-cadherin, fibronectin, N-cadherin and vimentin. Results: 101 patients enrolled into this study and 97 had enough tissue to perform the EMT examination. The median age was 59 years old, male/female:56/45, never smoker/smoker: 71/30, adenocarcinoma/non-adeno: 73/28, PS 0-1/2-3: 83/18, Stage IIIB/IV: 2/99, 1st /2nd-4th line: 13/88. The response rate and progression free survival(PFS) in the whole population were 45.5% and 7.6 months respectively. EMT test revealed that 46(47.4%) samples were epithelial phenotype, while 51(52.6%) were mesenchymal phenotype. 38 of 79 patients harbour activating EGFR mutation. Among the patients with EGFR wild type or unknown status, patients with an epithelial phenotype had a higher response rate(40% Vs 17.6%, P=0.056) and significantly longer PFS(7.6 m Vs 3.8 m, P=0.045) than these with a mesenchymal phenotype. However, the response rate(85.7% Vs 64.7%, P=0.249) and PFS(15.2 m Vs 12.2 m, P=0.420) were similar in the patients with activated EGFR mutation. Conclusions: Patients with an epithelial phenotype got more benefit from the treatment of EGFR-TKIs in the advanced EGFR wild type NSCLC patients, which indicated that the EMT might be a potential marker to guide the individual therapy of EGFR-TKIs in this subpopulation.