Prognostic and Predictive Implications of EGFR Mutations, EGFR Copy Number and KRAS Mutations in Advanced Stage Lung Adenocarcinoma

Background/Aim: Gefitinib and erlotinib were shown to be particularly effective in a clinically selected subpopulation of non-small cell lung cancer patients (NSCLC): adenocarcinoma histology, non-smoking status, Asian origin and female gender have been associated with improved clinical benefit compared to the unselected NSCLC population. The aim of the present study was to investigate the prognostic and predictive role of EGFR and KRAS analysis in advanced lung adenocarcinomas, selected according to clinical features associated to better response to EGFR tyrosine kinase inhibitors (TKIs), namely female gender and non-smoker or former light smoker status. Patients and Methods: EGFR and KRAS mutations and EGFR FISH status were assessed in 67 surgical samples. Results: EGFR and KRAS mutations were found in 16 (26.7%) and 12 (17.9%) patients, respectively. FISH analysis was positive in 34 (56.7%) patients. EGFR-mutated patients showed significantly longer survival when treated with EGFR TKIs (p=0.002. hazard ratio (HR)=0.036, 95% confidence interval (CI): 0.004 -0.303). KRAS mutations was found to be an independent negative prognostic factor in multivariate analysis (p=0.008, HR=3.52, 95%CI: 1.39-8.9). The prognostic value of EGFR FISH status was not confirmed in multivariate analysis (p=0.048, HR=0.47, 95%CI: 0.22-0.99). Conclusion: In a group of clinically selected patients, EGFR and KRAS analysis was able to define distinct molecular subsets of lung adenocarcinoma.