Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation

J Hepatobiliary Pancreat Sci. 2016 Jul;23(7):414-21. doi: 10.1002/jhbp.356. Epub 2016 Jun 12.

Abstract

Background: The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression.

Methods: Ninety-four HCC lesions no larger than 8 cm from 94 patients were immuno-histochemically studied using two hepatocyte markers (Hep par 1 and α-fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c-Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0-5.0 cm; S3, 5.0-8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined.

Results: The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c-Kit).

Conclusion: Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.

Keywords: Hepatocellular carcinoma; Immunohistochemistry; Progenitor cell; Stem cell; Transdifferentiation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Carcinoembryonic Antigen / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Cell Differentiation / physiology*
  • Female
  • Hepatectomy / methods
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Humans
  • Immunohistochemistry
  • Keratin-7 / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Proto-Oncogene Proteins c-kit / metabolism
  • Sampling Studies
  • Sensitivity and Specificity
  • Tumor Burden / physiology*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Keratin-7
  • Proto-Oncogene Proteins c-kit