The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type

J Clin Pathol. 2016 Oct;69(10):846-51. doi: 10.1136/jclinpath-2015-203491. Epub 2016 Mar 11.

Abstract

Aims: The WHO classification describes that combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell subtype (CHC-INT) is composed of tumour cells with features intermediate between hepatocytes and cholangiocytes. However, we previously reported that CHC-INT showed a high positive rate of biliary markers, but the expression of hepatocyte paraffin (HepPar)-1 was low. In this study, we examined the expression of other hepatocyte markers, such as arginase-1 (Arg-1), keratin (K) 8 and K18 in CHC-INT in order to examine the utility of pathological diagnosis in CHC-INT.

Methods: We performed immunohistochemistry (IHC) of Arg-1, K8 and K18 using 32 previously diagnosed as CHC-INT. Immunoreactivity was evaluated with grading from 0 to 4 according to the distribution area of positive cells. The obtained findings of Arg-1, K8 and K18 were compared with those of K7, K19 and HepPar-1.

Results: Out of the 32 cases, 22 (68.8%) cases were positive for Arg-1. Twenty-five (78.1%) were positive for K8. The IHC scores of Arg-1 and K8 were significantly higher than those of HepPar-1, but significantly lower than those of K7 and K19. The K18 expression was widely observed in all cases (100%). The IHC score of Arg-1 and K8 in CHC-INT was intermediate between hepatocellular carcinoma and cholangiocarcinoma.

Conclusions: Arg-1 and K8 were good markers to identify intermediate cells between hepatocytes and cholangiocytes. These can be useful markers for pathological diagnosis of CHC-INT, which usually has wide histological diversities, in combination with other hepatocytic and/or cholangiocytic markers.

Keywords: IMMUNOHISTOCHEMISTRY; KERATIN; LIVER CANCER.

MeSH terms

  • Aged
  • Arginase / metabolism*
  • Bile Duct Neoplasms / diagnosis
  • Bile Duct Neoplasms / metabolism*
  • Biomarkers / metabolism
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / metabolism*
  • Cholangiocarcinoma / diagnosis
  • Cholangiocarcinoma / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Keratin-18 / metabolism
  • Keratin-8 / metabolism
  • Keratins / genetics
  • Keratins / metabolism*
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged

Substances

  • Biomarkers
  • KRT18 protein, human
  • KRT8 protein, human
  • Keratin-18
  • Keratin-8
  • Keratins
  • ARG1 protein, human
  • Arginase