Differential expression of the anterior gradient protein-2 is a conserved feature during morphogenesis and carcinogenesis of the biliary tree
The anterior gradient protein-2 (AGR2) is overexpressed in numerous tumours such as breast, prostate or pancreas carcinomas and recently reported in fibrolamellar hepatocellular carcinoma (HCC). In the present study, we further describe AGR2 expression patterns all along the adult and fetal biliary tree and in cholangiocarcinomas. Immunohistochemistry using anti-AGR2 antibodies was performed in adult and fetal livers, gallbladders as well as cholangiocarcinomas and HCCs. In adult and fetal liver, the tall epithelial cells covering the large bile ducts as well as gallbladder epithelial cells showed strong AGR2 staining. Hilar and extrahepatic cholangiocarcinomas, and a subset of intrahepatic cholangiocarcinomas, which displayed a morphological mucus-excreting feature, also displayed AGR2 expression. In contrast, AGR2 expression was not detected in typical HCCs. Our study shows that the differential expression of AGR2 is a phenotypic feature of the cholangiocytes covering different segments of the biliary tree. This pattern of expression is conserved during fetal and adult life, as well as during biliary carcinogenesis.