title: Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression.
abstract: Viral hepatitis-associated intrahepatic cholangiocarcinoma is thought to have common disease processes with hepatocellular carcinoma, but until now the histomorphological and genetic features of viral hepatitis-associated intrahepatic cholangiocarcinoma is still unknown. From 2000 to 2010, 170 patients with intrahepatic cholangiocarcinoma who received detailed pathological assessment and regular follow-up at the National Taiwan University Hospital were selected for this study. Of 170 patients, 69 (41%) were positive for hepatitis B and/or C virus. These patients were younger, were more frequently male, and had elevated serum α-fetoprotein levels as compared with seronegative intrahepatic cholangiocarcinoma patients. Grossly these tumors were mostly of the mass-forming type, and histologically, cholangiolar differentiation was more frequently seen. We identified N-cadherin as an immunohistochemical marker strongly associated with hepatitis virus infection. The prevalence of viral hepatitis in patients with N-cadherin-positive intrahepatic cholangiocarcinoma was 75%, and that in N-cadherin-negative patients was only 37%. N-cadherin-positive patients were younger, had elevated α-fetoprotein, and had no hepatolithiasis. All N-cadherin-positive intrahepatic cholangiocarcinomas were of the mass-forming type. N-cadherin positivity was strongly associated with cholangiolar morphology and lack of carcinoembryonic antigen and MUC2 expression, whereas K-RAS mutations were less frequent. Our results indicate that a subgroup of intrahepatic cholangiocarcinoma characterized by cholangiolar differentiation and N-cadherin expression is strongly associated with viral hepatitis.
authors.affiliation: Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
authors.forename: Tsan-Hua
authors.initials: TH
authors.lastname: Yu
authors.forename: Ray-Hwang
authors.initials: RH
authors.lastname: Yuan
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Wan-Ching
authors.initials: WC
authors.lastname: Yang
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
mesh_terms: D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D054338:Cell Transdifferentiation; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005260:Female; D011905:Genes, ras; D006509:Hepatitis B / Q000150:complications / Q000473:pathology; D006526:Hepatitis C / Q000150:complications / Q000473:pathology; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D000509:alpha-Fetoproteins