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

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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. ©American Society for Clinical Pathology.

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Sartori, G., Cavazza, A., Bertolini, F., Longo, L., Marchioni, A., Costantini, M., … Rossi, G. (2008). A subset of lung adenocarcinomas and atypical adenomatous hyperplasia-associated foci are genotypically related: An EGFR, HER2, and K-ras mutational analysis. American Journal of Clinical Pathology, 129(2), 202–210. https://doi.org/10.1309/THU13F3JRJVWLM30

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