Molecular changes of epidermal growth factor receptor (EGFR) and KRAS and their impact on the clinical outcomes in surgically resected adenocarcinoma of the lung

Abstract

Recent studies have reported that clinical response to epidermal growth factor receptor (EGFR) inhibitors is associated with somatic changes of EGFR in the advanced stage of lung cancer. However, there is no clear data demonstrating whether such molecular changes of EGFR per se can affect the clinical outcome of early stage cancer after surgical resection. DNA mutations of EGFR and KRAS were investigated in 71 adenocarcinoma patients who received surgical resection. Fluorescence in situ hybridization (FISH) of EGFR gene amplification was performed in 48 samples. We detected EGFR mutations in 25 patients (35.2%). EGFR mutation was more frequently found in cases with BAC features (13/22 (59.1%):13/49 (26.5%); p=0.008) and in non-smokers (19/41 (46.3%):7/30 (23.3%); p=0.047). However, the EGFR mutation was not associated with age, gender, or clinical stage. The amplification of EGFR copy was frequently observed in the female gender (12/29 (41.4%):3/19 (15.8%); p=0.061) and in the advanced stage (> or =Stage IIIA, 9/19 (47.4%):6/29 (20.7%); p=0.051). KRAS mutations were present in five patients (7.0%) and none of them showed EGFR mutation. KRAS mutations (p=0.000), male gender (p=0.001), absence of BAC feature (p=0.003), advanced stage (p=0.039), and smoking history (p=0.030) were poor prognostic factors for overall survival, whereas EGFR mutation (p=0.184) and amplification (p=0.756) were not. The presence of EGFR mutation was not a prognostic factor of the clinical outcome of early lung cancer after surgical resection. This result provides an important message for the protocol design of future trials of EGFR inhibitors in early lung cancer. As the KRAS mutation was a poor prognostic factor and it presents reciprocally with EGFR mutation, KRAS mutation should be investigated in such trials. DNA mutations of EGFR and KRAS were investigated in 71 adenocarcinoma patients who received surgical resection. Whereas KRAS mutation was a poor prognostic factor, EGFR mutation was not, and its presence per se did not affect the clinical outcome of early lung cancer after surgical resection.