Phenotypic characterization of early biliary tract carcinomas proposes two carcinogenesis pathways

Abstract

    Early biliary tract carcinomas (BTCs) are divided into three groups: early gallbladder carcinoma (GBC), early extrahepatic bile duct carcinoma (EBC), and early duodenal ampullary carcinoma (DAC). These early carcinomas frequently show metaplastic changes. However, phenotypic characterization has not yet been examined. We examined 76 lesions of surgically resected early biliary tract carcinomas (pTis/pT1 tumors according to TNM classification). The predominant carcinoma phenotypes were classified with hematoxylin and eosin (HE) stain, and immunohistochemical examinations (MUC1, MUC2, MUC5AC, MUC6, and CD10) were performed. We also analyzed phenotypes of the surrounding non-neoplastic mucosa. Of the 33 early GBCs, 18 (54.5%) were biliary type, and 15 (45.5%) were metaplastic type （gastric foveolar type/intestinal type） carcinoma. Of the 26 early EBCs, 18 (69.2%) were biliary type carcinoma, and eight (30.8%) were metaplastic type carcinoma. Of the 17 early DACs, eight (47.1%) were biliary type carcinoma, nine (52.9%) were metaplastic type carcinoma. Biliary type carcinomas less frequently showed metaplastic changes, while metaplastic type carcinomas were frequently surrounded by the metaplastic mucosa. Early GBC and early DAC more frequently showed metaplastic changes, compared to the early EBC. In conclusion, we speculated that two carcinogenesis pathways of early BTC (GBC, EBC, and DAC): (1) carcinomas arising from the proper epithelium (mainly EBC) and (2) carcinomas from the metaplastic epithelium (mainly GBC and DAC).