In this study, we examined EGFR and KRAS gene mutations in 119 synchronous pulmonary lesions, including 40 precursor lesions (atypical adenomatous hyperplasia, AAH), 26 carcinomas in situ (non-mucinous bronchioloalveolar carcinoma, BAC), 14 minimally invasive adenocarcinomas, 34 overt invasive adenocarcinomas, and five of other subtypes of cancer.
These results suggest that carcinogenesis in the biliary tract epithelium in APBDU is accompanied by multistep genetic mutational events; K-ras gene mutation occurs early in epithelial hyperplasia or metaplasia, whereas inactivation of the DPC-4 gene accumulates late in the progression of biliary tract adenocarcinoma.