TY - JOUR
T1 - A subset of lung adenocarcinomas and atypical adenomatous hyperplasia-associated foci are genotypically related
T2 - An EGFR, HER2, and K-ras mutational analysis
AU - Sartori, Giuliana
AU - Cavazza, Alberto
AU - Bertolini, Federica
AU - Longo, Lucia
AU - Marchioni, Alessandro
AU - Costantini, Matteo
AU - Barbieri, Fausto
AU - Migaldi, Mario
AU - Rossi, Giulio
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - Adenocarcinoma
KW - Atypical adenomatous hyperplasia
KW - EGFR
KW - Epidermal growth factor receptor
KW - HER2
KW - K-ras
KW - Lung
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UR - http://www.scopus.com/inward/citedby.url?scp=40449103502&partnerID=8YFLogxK
U2 - 10.1309/THU13F3JRJVWLM30
DO - 10.1309/THU13F3JRJVWLM30
M3 - Article
C2 - 18208799
AN - SCOPUS:40449103502
VL - 129
SP - 202
EP - 210
JO - American Journal of Clinical Pathology
JF - American Journal of Clinical Pathology
SN - 0002-9173
IS - 2
ER -