N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas

Mod Pathol. 2009 Feb;22(2):182-90. doi: 10.1038/modpathol.2008.123. Epub 2008 Jul 11.


As a definite immunoprofile of this tumor is missing, the histopathologic diagnosis of intrahepatic cholangiocarcinoma is difficult. The aim of this study was to explore E- and N-cadherin expressions in intrahepatic bile duct tumors, and to determine their potential interest in differential diagnosis. Normal liver tissue, 5 cirrhosis with ductular reaction, 5 focal nodular hyperplasia, 5 bile duct hamartomas, 5 bile duct adenomas, and 45 intrahepatic cholangiocarcinomas from Caucasian patients were studied. Tissue-microarrays including 20 esophageal, 86 gastric, 8 small bowel, 64 colonic, 18 pancreatic, 6 gallbladder, and 7 extrahepatic biliary tract adenocarcinomas, 22 hepatocellular carcinomas, and normal tissues were constructed. Immunohistochemistry was performed using E-cadherin, N-cadherin, NCAM, Hep Par1, and cytokeratins 7, 19 and 20. Immunoblot analysis of frozen liver tissues was performed to control the specificity of E- and N-cadherin antibodies used. In normal liver, epithelial cells of intrahepatic bile ducts, whatever their caliber, as well as hepatocytes, coexpressed E- and N-cadherins at their plasma membranes. In cirrhosis, ductular reactions completely expressed E- and N-cadherins. All the benign lesions and 30 of the 45 intrahepatic cholangiocarcinomas (23/29 peripheral and 7/16 hilar) also expressed N-cadherin. E-cadherin was detected in all the lesions. The expression of N-cadherin at the plasma membrane of tumor cells was significantly more frequent in peripheral than in hilar intrahepatic cholangiocarcinomas (P=0.003). Among noncholangiocarcinomas, only 1% gastric and 66% gallbladder adenocarcinomas and all the hepatocellular carcinomas expressed N-cadherin at the membrane of tumor cells. Finally, for the diagnosis of intrahepatic cholangiocarcinomas, the specificity value of membranous expression of N-cadherin was 88%, whereas that of the combination cytokeratin 7/membranous N-cadherin was 98%. In the gastrointestinal and liver tract, membranous N-cadherin is restricted to the hepatocytes and intrahepatic biliary cells. In combination with cytokeratin 7 and Hep Par1, N-cadherin is a reliable tool for the histopathological diagnosis of primary hepatic tumors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis*
  • Bile Duct Neoplasms / immunology*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / immunology*
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers, Tumor / analysis*
  • Cadherins / analysis*
  • Cholangiocarcinoma / immunology*
  • Cholangiocarcinoma / pathology
  • Diagnosis, Differential
  • Female
  • France
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Keratin-7 / analysis
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Reproducibility of Results
  • Tissue Array Analysis


  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • KRT7 protein, human
  • Keratin-7