Frequent EGFR mutations in noninvasive bronchioloalveolar carcinoma.

Mutations of the epidermal growth factor receptor gene (EGFR) have been reported to be present in a considerable fraction of lung adenocarcinomas showing dramatic response to EGFR tyrosine kinase inhibitors. To clarify pathogenic significance of the mutations for the development of lung adenocarcinoma, we investigated stage I lung adenocarcinomas for the mutations. First, 107 cases of macrodissected stage I adenocarcinomas were examined for mutations in exons 18-21 of the EGFR gene. EGFR mutations were detected in 36 of the 107 cases (34%). In particular, among the stage I cases, the mutations were detected in 17 of 42 small-sized adenocarcinomas (<or=2 cm in diameter) (40%), including 7 of 11 noninvasive bronchioloalveolar carcinomas (BACs) (64%) and 7 of 25 invasive adenocarcinomas with BAC components (28%). Second, 26 cases of laser capture microdissected small-sized adenocarcinomas, including 9 cases in the first analysis, were examined for the mutations. Reanalysis of microdissected materials in the 9 cases identified the mutations in 2 more adenocarcinomas with BAC components. Moreover, in the analysis of the other 17 microdissected materials, EGFR mutations were detected in 7 of 12 BACs (58%) and in 3 of 5 adenocarcinomas with BAC components (60%). EGFR mutations are present frequently in BACs, and are thus likely to be a critical genetic alteration for the formation of noninvasive lung adenocarcinoma.