title: Frequent EGFR mutations in noninvasive bronchioloalveolar carcinoma.
abstract: Mutations of the epidermal growth factor receptor gene (EGFR) have been reported to be present in a considerable fraction of lung adenocarcinomas showing dramatic response to EGFR tyrosine kinase inhibitors. To clarify pathogenic significance of the mutations for the development of lung adenocarcinoma, we investigated stage I lung adenocarcinomas for the mutations. First, 107 cases of macrodissected stage I adenocarcinomas were examined for mutations in exons 18-21 of the EGFR gene. EGFR mutations were detected in 36 of the 107 cases (34%). In particular, among the stage I cases, the mutations were detected in 17 of 42 small-sized adenocarcinomas (<or=2 cm in diameter) (40%), including 7 of 11 noninvasive bronchioloalveolar carcinomas (BACs) (64%) and 7 of 25 invasive adenocarcinomas with BAC components (28%). Second, 26 cases of laser capture microdissected small-sized adenocarcinomas, including 9 cases in the first analysis, were examined for the mutations. Reanalysis of microdissected materials in the 9 cases identified the mutations in 2 more adenocarcinomas with BAC components. Moreover, in the analysis of the other 17 microdissected materials, EGFR mutations were detected in 7 of 12 BACs (58%) and in 3 of 5 adenocarcinomas with BAC components (60%). EGFR mutations are present frequently in BACs, and are thus likely to be a critical genetic alteration for the formation of noninvasive lung adenocarcinoma.
authors.affiliation: Biology Division, National Cancer Center Research Institute, Tokyo, and Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D066246:ErbB Receptors