Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma

Int J Clin Pract. 2008 Aug;62(8):1212-8. doi: 10.1111/j.1742-1241.2008.01777.x. Epub 2008 May 8.


Background: Although the primitive haematopoietic and neuronal stem cell marker CD133 is known to be present in cancer stem cells (CSCs) in hepatocellular carcinoma (HCC), the postresection prognostic impact of CD133 in HCC patients remains limited.

Methods: Sixty-three resected specimens were collected from HCC patients. The expression of CD133 protein was analysed by immunohistochemistry and the association of CD133 expression with clinicopathological characteristics, tumour recurrence and survival of the patients was evaluated.

Results: Immunohistochemical analysis of 63 HCC tissue specimens revealed that CD133 positive tumour cells were frequently present in HCC. Increased CD133 immunostaining was found in 26 specimens (41.3%). Increased CD133 expression levels were correlated with increased tumour grade, advanced disease stage, and elevated serum alpha-fetoprotein levels. Kaplan-Meier analysis indicated that patients with increased CD133 levels had shorter overall survival and higher recurrence rates compared with patients with low CD133 expression. Multivariate analyses revealed that increased CD133 expression was an independent prognostic factor for survival and tumour recurrence in patients with HCC.

Conclusions: These findings suggest that reactivated CD133 positive cells are frequently present in HCC. Additionally, increased CD133 expression corresponds with higher stage tumours in HCC, thus indicating a poor prognosis for patients. These data support the CSC hypothesis.

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Glycoproteins / metabolism*
  • Hepatectomy / methods*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Neoplastic Stem Cells / pathology
  • Peptides / metabolism*
  • Survival Rate


  • AC133 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • Glycoproteins
  • PROM1 protein, human
  • Peptides