Canalicular immunostaining of neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas

Am J Surg Pathol. 2001 Oct;25(10):1297-303. doi: 10.1097/00000478-200110000-00011.


Neprilysin (CD10) is expressed in both normal and neoplastic liver tissue, where it exhibits a characteristic canalicular pattern (CD10can) similar to the one observed when antibodies cross-react with biliary glycoprotein I (p-CEA). The aim of this retrospective study was to investigate the use of CD10can in differentiating between hepatocellular carcinomas (HCCs; 63 specimens) and nonhepatocellular carcinomas (non-HCCs) metastatic to the liver (non-HCC; 25 specimens). Immunostaining was performed with antibodies directed against CD10, p-CEA, and alpha-fetoprotein (AFP). Albumin mRNA was detected by nonradioactive in situ hybridization (ISHalbumin). In the HCC group a canalicular staining pattern for CD10 was found in 43 (68.3%) specimens. AFP was found in 15 (23.8%) specimens, and a canalicular staining pattern for p-CEA was present in 60 (95.2%) specimens. ISHalbumin was performed in 35 HCC specimens and showed labeling of tumor cells in 30 (85.7%) specimens. In the non-HCC group, CD10can, and p-CEA, immunostaining for AFP and labeling for ISHalbumin were confined to non-neoplastic liver tissue. Sensitivity and specificity were, respectively, 68.3% and 100% for CD10can, 23.8% and 100% for AFP, 95.2% and 100% for canalicular p-CEA, and 86.4% and 100% for ISHalbumin. Our results demonstrate that canalicular staining for CD10 is a highly specific marker of hepatocytic differentiation. Although it does not differentiate between benign and malignant lesions, CD10can is clearly useful in differentiating between HCC and non-HCC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Canaliculi / chemistry
  • Bile Canaliculi / enzymology*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Diagnosis, Differential
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neprilysin / analysis
  • Neprilysin / metabolism*
  • Retrospective Studies


  • Biomarkers, Tumor
  • Neprilysin