Utility of an immunohistochemical panel consisting of glypican-3, heat-shock protein-70, and glutamine synthetase in the distinction of low-grade hepatocellular carcinoma from hepatocellular adenoma

Appl Immunohistochem Mol Morphol. 2013 Mar;21(2):170-6. doi: 10.1097/PAI.0b013e31825d527f.

Abstract

Background: The pathologic distinction between hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA) is sometimes problematic due to histologic overlap between the 2 entities, a problem amplified on small biopsy specimens. Several recently characterized immunohistochemical markers such as glypican-3 (GPC-3), heat-shock protein-70 (HSP-70), and glutamine synthetase (GS) help distinguish dysplastic nodules from HCC. The utility of this panel in the distinction of low-grade hepatocellular carcinoma (LG-HCC) from HCA has not been fully described.

Objective: To determine whether the above markers are useful in the distinction of HCCs from HCAs.

Design: Tissue microarrays were constructed with 30 LG-HCCs and 18 HCAs. The arrays were stained with the above markers and analyzed with respect to amount and pattern of staining. GPC-3 and HSP-70 were considered positive when 10% of tumor cells showed immunoreactivity. GS was considered positive when 50% of tumor cells showed immunoreactivity.

Results: GPC-3 was positive in 13 of 30 LG-HCCs and 0 of 18 adenomas. The sensitivity was 43% and the specificity was 100%. HSP-70 was positive in 14 of 30 LG-HCCs and 0 of 18 adenomas. The sensitivity was 46% and the specificity was 100%. GS was positive in 24 of 30 LG-HCCs and 9 of 18 adenomas. The sensitivity was 80% and the specificity was 50%.

Conclusions: GPC-3 and HSP-70 are helpful in separating carcinomas from adenomas. GS is not useful in this clinical context.

MeSH terms

  • Adenoma, Liver Cell / diagnosis*
  • Adenoma, Liver Cell / genetics
  • Adenoma, Liver Cell / metabolism
  • Adenoma, Liver Cell / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Child
  • Diagnosis, Differential
  • Female
  • Gene Expression
  • Glutamate-Ammonia Ligase / genetics*
  • Glutamate-Ammonia Ligase / metabolism
  • Glypicans / genetics*
  • Glypicans / metabolism
  • HSP70 Heat-Shock Proteins / genetics*
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • GPC3 protein, human
  • Glypicans
  • HSP70 Heat-Shock Proteins
  • Glutamate-Ammonia Ligase