Expression of stemness markers (CD133 and EpCAM) in prognostication of hepatocellular carcinoma

Histopathology. 2014 Jun;64(7):935-50. doi: 10.1111/his.12342. Epub 2014 Feb 7.

Abstract

Aims: The expression of stemness markers in hepatocellular carcinoma (HCC) is suggested to be associated with poor clinical outcome after surgical resection. There are few data on their independent prognostic role in addition to the existing AJCC TNM staging system.

Methods and results: The immunohistochemical expression of CD133, EpCAM, CK19 and CD56 was studied in a cohort of 282 surgical specimens collected from patients undergoing resection of primary HCC. CD133-positive HCCs were usually smaller in size (P = 0.002) and arose more frequently in cirrhotic liver (P = 0.002). CD133 expression was an independent prognostic factor for overall survival (hazard ratio 2.30, P < 0.001), and a highly potent prognostic factor in patients with stage I disease (hazard ratio 3.91, P = 0.001). EpCAM expression was associated with younger age (P < 0.001), smaller tumour size (P = 0.018) and poorer histological differentiation (P = 0.042). EpCAM immunoreactivity was an independent factor for disease-free survival in HCCs at all stages (hazard ratio 2.05, P = 0.001), stage II (hazard ratio 3.66, P = 0.010) and stages III/IV (hazard ratio 3.22, P = 0.001). Neither CK19 nor CD56 offered any independent prognostic value.

Conclusion: The prognostic role of CD133 was most significant in TNM stage I disease, while the prognostic role of EpCAM was more apparent in more advanced TNM stages.

Keywords: AJCC TNM stage; CD133; EpCAM; hepatocellular carcinoma; stemness marker.

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Adhesion Molecules / metabolism*
  • Cohort Studies
  • Disease-Free Survival
  • Epithelial Cell Adhesion Molecule
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / metabolism*
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Peptides / metabolism*
  • Prognosis

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Glycoproteins
  • PROM1 protein, human
  • Peptides