Immunohistochemical detection of bcl-2 protein in normal and pathological human liver

Am J Pathol. 1994 Mar;144(3):460-5.


The bcl-2 protein, which prolongs cell survival by blocking apoptosis, is expressed by progenitor cells in several self-renewing tissues and by tumoral cells in some extrahepatic neoplasms. Because the liver is a slow self-renewing tissue, an immunohistochemical study of the cellular distribution of the bcl-2 protein was performed in normal liver (12 cases), nontumoral hepatic lesions (33 cases), and benign or malignant liver tumors (46 cases). In normal liver, bcl-2 was expressed by bile ductules and small bile duct epithelium, but not by hepatocytes or large bile duct epithelium. In cirrhosis and focal nodular hyperplasia, epithelial cells of the ductular proliferation were bcl-2-positive. Eight of 11 cholangiocarcinomas stained positively for bcl-2, whereas all 15 hepatocellular carcinomas were bcl-2-negative. bcl-2 was also expressed in 6 of 14 metastatic adenocarcinomas. These findings suggest that the ductular cells and small bile duct epithelial cells might have a prolonged survival and might be hepatic progenitor cells. In addition, the bcl-2 protein appears to be a marker of cholangiocarcinoma but not of hepatocellular carcinoma and could help in distinguishing between these two primary liver tumors.

Publication types

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

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Bile Duct Neoplasms / chemistry
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / chemistry
  • Bile Ducts, Intrahepatic / cytology
  • Bile Ducts, Intrahepatic / pathology
  • Carcinoma, Hepatocellular / chemistry*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Division
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Cholestasis / metabolism
  • Cholestasis / pathology
  • Epithelial Cells
  • Epithelium / chemistry
  • Epithelium / pathology
  • Humans
  • Immunohistochemistry
  • Liver / chemistry*
  • Liver / cytology
  • Liver / pathology
  • Liver Diseases / metabolism*
  • Liver Diseases / pathology
  • Liver Neoplasms / chemistry*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2