A subset of lung adenocarcinomas and atypical adenomatous hyperplasia-associated foci are genotypically related: An EGFR, HER2, and K-ras mutational analysis

Giuliana Sartori, Alberto Cavazza, Federica Bertolini, Lucia Longo, Alessandro Marchioni, Matteo Costantini, Fausto Barbieri, Mario Migaldi, Giulio Rossi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)202-210
Number of pages9
JournalAmerican Journal of Clinical Pathology
Volume129
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Adenocarcinoma
  • Atypical adenomatous hyperplasia
  • EGFR
  • Epidermal growth factor receptor
  • HER2
  • K-ras
  • Lung

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'A subset of lung adenocarcinomas and atypical adenomatous hyperplasia-associated foci are genotypically related: An EGFR, HER2, and K-ras mutational analysis'. Together they form a unique fingerprint.

Cite this