Application of Immunohistochemistry in the Pathological Diagnosis of Liver Tumors

Int J Mol Sci. 2021 May 28;22(11):5780. doi: 10.3390/ijms22115780.

Abstract

Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite pathological diagnosis cannot be obtained by histological evaluation alone, especially when the sample is a small biopsy; in such cases, immunohistochemical staining is very useful. Immunohistochemistry is the most frequently used technique for molecular pathological diagnosis due to its broad application, ease of performance and evaluation, and reasonable cost. The results occasionally reflect specific genetic mutations. The immunohistochemical markers of hepatocellular carcinoma include those of hepatocellular differentiation-such as hepatocyte paraffin 1 and arginase-1-and those of malignant hepatocytes-such as glypican-3, heat shock protein 70, and glutamine synthetase (GS). To classify the subtypes of hepatocellular adenoma, examination of several immunohistochemical markers, such as liver fatty acid-binding protein, GS, and serum amyloid A, is indispensable. Immunohistochemical staining for GS is also important for the diagnosis of focal nodular hyperplasia. The representative immunohistochemical markers of intrahepatic cholangiocarcinoma include cytokeratin (CK) 7 and CK19. In this article, we provide an overview of the application of immunohistochemistry in the pathological diagnosis of liver tumors referring to the association with genetic alterations. Furthermore, we aimed to explain the practical points in the differential diagnosis of liver tumors by immunohistochemical staining.

Keywords: focal nodular hyperplasia; hepatocellular adenoma; hepatocellular carcinoma; immunohistochemical staining; intrahepatic cholangiocarcinoma; liver tumor.

Publication types

  • Review

MeSH terms

  • Adenoma, Liver Cell / diagnosis
  • Adenoma, Liver Cell / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / metabolism*
  • Cholangiocarcinoma / diagnosis
  • Cholangiocarcinoma / metabolism*
  • Diagnosis, Differential
  • Glypicans / metabolism
  • Humans
  • Immunohistochemistry / methods*
  • Keratin-7 / metabolism
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism*

Substances

  • Biomarkers, Tumor
  • Glypicans
  • Keratin-7