Viral Hepatitis Is Associated with a Distinct Subtype of Intrahepatic Cholangiocarcinoma Characterized by Cholangiolar Differentiation and N-Cadherin Expression.
Yung-Ming Jeng. National Taiwan University Hospital, Taipei, Taiwan
Background: Viral hepatitis-associated intrahepatic cholangiocarcinoma is thought to have common disease processes with hepatocellular carcinoma, but until now there has been no morphological or molecular evidence to support this hypothesis. The study was performed to identify distinct clinicopathological and molecular characteristics of viral hepatitis-associated intrahepatic cholangiocarcinoma.
Design: 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. Immunophenotypic features were examined by immunohistochemical stain. Detection of K-ras and BRAF gene mutation was performed by polymerase chain reaction and direct sequencing.
Results: Of 170 ICC diagnosed between 2000 and 2010 in Taiwan, 69 (40.6%) were positive for hepatitis B and/or C virus. These patients were younger, were more frequently male, and had elevated serum alpha-fetoprotein levels as compared with seronegative ICC 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 ICC was 70.9%; that in N-cadherin-negative patients was only 33%. N-cadherin-positive patients were younger, had elevated AFP, and had no hepatolithiasis. All N-cadherin-positive ICCs were of the mass-forming type. N-cadherin positivity was strongly associated with cholangiolar morphology and lack of carcinoembryonic antigen and Muc-2 expression, while K-RAS mutations were less frequent.
Conclusions: A subgroup of ICC characterized by cholangiolar differentiation and N-cadherin expression is strongly associated with viral hepatitis.
Category: Liver & Pancreas
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 267, Tuesday Morning