title: Epidermal growth factor receptor gene mutations in atypical adenomatous hyperplasias of the lung.
abstract: Activating epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung adenocarcinomas, especially adenocarcinomas with a nonmucinous bronchioloalveolar carcinoma component. EGFR-mutated lung adenocarcinomas respond well to EGFR tyrosine kinase inhibitors. We previously found that most (88%) pure nonmucinous bronchioloalveolar carcinomas (adenocarcinoma in situ) already harbor EGFR mutations, indicating that the mutations are an early genetic event in the pathogenesis. We examined 54 atypical adenomatous hyperplasias, precursor lesions of lung adenocarcinomas, obtained from 28 Japanese patients for the hotspot mutations of EGFR exons 19 and 21 and K-ras codon 12. EGFR mutations were observed in 17 of the 54 (32%) atypical adenomatous hyperplasias examined: Ten and seven atypical adenomatous hyperplasias had deletion mutations at exon 19 or point mutations (L858R) at exon 21, respectively. We did not observe apparent histological differences between atypical adenomatous hyperplasias with and without EGFR mutations. K-ras mutation (G12S) was detected in only one atypical adenomatous hyperplasia. As EGFR mutational frequency of atypical adenomatous hyperplasias was much lower than that of nonmucinous bronchioloalveolar carcinomas, we surmise that EGFR-mutated atypical adenomatous hyperplasias, but not atypical adenomatous hyperplasias with wild-type EGFR, are likely to progress to nonmucinous bronchioloalveolar carcinomas.
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Shoichi
authors.initials: S
authors.lastname: Matsukuma
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics* / Q000473:pathology; D018255:Adenomatosis, Pulmonary / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D003062:Codon; D004252:DNA Mutational Analysis; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D006965:Hyperplasia; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D003062:Codon; C512478:EGFR protein, human; D066246:ErbB Receptors