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

• Published in: Clinical cancer research Vol. 11; no. 3; pp. 1167 - 1173
• Main Authors: TOKUMO, Masaki, TOYOOKA, Shinichi, TABATA, Masahiro, UEOKA, Hiroshi, TANIMOTO, Mitsune, DATE, Hiroshi, GAZDAR, Adi F, SHIMIZU, Nobuyoshi, KIURA, Katsuyuki, SHIGEMATSU, Hisayuki, TOMII, Kunitoshi, AOE, Motoi, ICHIMURA, Kouichi, TSUDA, Toshihide, YANO, Masaaki, TSUKUDA, Kazunori
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.02.2005
• Subjects: Adult; Aged; Amino Acid Sequence; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Base Sequence; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; DNA Mutational Analysis; DNA, Neoplasm - chemistry; DNA, Neoplasm - genetics; EGFR; Female; gefitinib; Humans; lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Mutation; Pharmacology. Drug treatments; Pneumology; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - genetics; Sequence Homology, Amino Acid; Smoking; Survival Analysis; Treatment Outcome; Tumors of the respiratory system and mediastinum; Lung disease; Growth factor receptor; Histopathology; Respiratory disease; Lung cancer; Clinical form; Bronchus disease; Genetics; Malignant tumor; Mutation; non-small cell lung carcinoma; Epidermal growth factor receptor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.1167.11.3

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.