Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival

J Hepatol. 2000 Jan;32(1):78-84. doi: 10.1016/s0168-8278(00)80192-0.


Background/aims: Members of the CD44 family are transmembrane glycoproteins which act mainly as receptors for hyaluronan. We have examined the expression of CD44s and several CD44v and the relationship between these and hepatocellular carcinoma (HCC) grade, clinicopathological parameters, p53 expression, and patient survival in HCC.

Methods: Formalin-fixed, paraffin-embedded tissue sections from 107 surgically resected HCC were examined immunohistochemically using a semi-quantitative scoring system to detect the expression of different forms of CD44.

Results: The number of CD44s-positive cases was 36 (34%), CD44v5 52 (49%), CD44v6 29 (27%), CD44v7-8 41 (38%), and CD44v10 26 (24%). Expression of these molecules correlated with high histological grade, being the highest in poorly-differentiated HCC. High CD44v6 expression significantly correlated with the presence of vascular invasion and p53 overexpression. Kaplan-Meier examination of patient survival revealed that HCC patients with positivity of each of these five molecules had a reduced survival rate, and that HCC patients positive for all the five CD44 molecules had worse survival than HCC patients positive for four or less of these CD44 molecules. In multivariate survival analysis, CD44s positivity was an independent factor. However, positivity for one or more CD44 isoforms was the most useful independent factor for overall survival.

Conclusion: These results suggest that up-regulation of CD44 isoforms is associated with poorly-differentiated HCC and shortened survival.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / immunology
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Immunoenzyme Techniques
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Protein Isoforms / metabolism
  • Survival Analysis
  • Survival Rate
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation


  • Antibodies, Monoclonal
  • Hyaluronan Receptors
  • Protein Isoforms
  • Tumor Suppressor Protein p53