The Relationship between Epidermal Growth Factor Receptor Mutations and Clinicopathologic Features in Non–Small Cell Lung Cancers

Abstract

Purpose: Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non–small cell lung cancers (NSCLC). Here, we investigated the relationship between EGFR mutation and clinicopathologic features. Experimental Design: EGFR mutational status of 120 NSCLCs was determined mainly in EGFR exons 18 to 21 by direct sequence and correlated with clinicopathologic parameters. Results: EGFR mutations were present in 38 cases (32%) and the majority of mutations were in-frame deletions of exon 19 (19 cases) and a missense mutation in exon 21 (18cases). EGFR mutations were frequently associated with adenocarcinoma (P < 0.0001), never smoker (P < 0.0001), and female gender (P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation (P < 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Furthermore, gender difference was observed for the mutational location (P = 0.01) dominance of exon 19 for males and exon 21 for females. Twenty-one cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib responsiveness (P = 0.002). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage; however, the difference was not significant. Conclusions: We show that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib responsiveness in NSCLC.