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

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.