title: A subset of lung adenocarcinomas and atypical adenomatous hyperplasia-associated foci are genotypically related: an EGFR, HER2, and K-ras mutational analysis.
abstract: Atypical adenomatous hyperplasia (AAH) is considered the preinvasive lesion of pulmonary adenocarcinoma, and mutations of EGFR, HER2, and K-ras are involved in the early stage of lung adenocarcinoma carcinogenesis, also predicting clinical response to anti-EGFR small molecule inhibitors. We analyzed 18 cases of primary lung adenocarcinoma with concomitant AAH foci from 13 patients for mutations of EGFR (exons 18-21), HER2 (exons 19-20), and K-ras (exon 2) by direct sequencing polymerase chain reaction. Among mutated cases, concordant mutations of EGFR or K-ras in adenocarcinoma and related AAH were observed in 5 (63%) of 8 cases. In particular, 3 of 4 adenocarcinomas with EGFR mutations (all L858R point mutations in women, never or former smokers) had a concomitant and identical mutation in AAH, and 2 of 4 adenocarcinomas with K-ras mutations (both at codon 12 in women, a never and a current smoker) showed the same mutation in concomitant AAH. All cases were wild-type for HER2. Mutations of EGFR and K-ras genes represent an early event in lung adenocarcinomagenesis, and AAH convincingly seems to be a precursor lesion in a subset of cases of adenocarcinoma.
authors.affiliation: Section of Pathologic Anatomy, Azienda Policlinico, Modena, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Sartori
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.forename: Federica
authors.initials: F
authors.lastname: Bertolini
authors.forename: Lucia
authors.initials: L
authors.lastname: Longo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marchioni
authors.forename: Matteo
authors.initials: M
authors.lastname: Costantini
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.forename: Mario
authors.initials: M
authors.lastname: Migaldi
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D018255:Adenomatosis, Pulmonary / Q000235:genetics; D000328:Adult; D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D006965:Hyperplasia / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011230:Precancerous Conditions / Q000235:genetics*
chemical_list: D066246:ErbB Receptors