title: Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung.
abstract: Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.
authors.affiliation: Department of Surgery II, Nagoya City University Medical School, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Haneda
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Endo
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Yukiue
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
chemical_list: D066246:ErbB Receptors