Expression of Wnt-5a and its clinicopathological significance in hepatocellular carcinoma

Dig Liver Dis. 2008 Jul;40(7):560-7. doi: 10.1016/j.dld.2007.12.011. Epub 2008 Feb 21.


Background: The functions of Wnt-5a in human cancers are controversial and unclear.

Aim: To investigate the clinical significance of Wnt-5a expression in hepatocellular carcinoma.

Patients and methods: Real-time quantitative Reverse transcriptase Polymerase Chain Reaction was done to evaluate Wnt-5a gene expression. Wnt-5a, beta-catenin, E-cadherin and Ki-67 were examined immunohistochemically in 114 hepatocellular carcinoma cases.

Results: Compared to normal tissue, Wnt-5a mRNA expression was clearly increased in hepatocellular carcinoma, chronic hepatitis and cirrhosis. On immunohistochemistry, immunostaining of Wnt-5a showed a bell-shaped pattern: low to undetectable levels were present in normal tissue and in tumour samples, whereas strong immunostaining was seen in chronic hepatitis, cirrhosis and dysplastic liver cells. Reduction or loss of Wnt-5a protein expression was found in 80.7% of hepatocellular carcinoma cases (n=92) and was significantly associated with higher tumour stage (p<0.001), serum AFP level (p=0.025), low membranous expression of E-cadherin (p<0.0001) and beta-catenin (p=0.036) and high Ki-67 labelling indices (LIs, p=0.001).

Conclusion: Wnt-5a mRNA and protein levels are higher than normal in hepatitis and cirrhosis and appear to be related to the presence of hepatitis B virus infection. However, Wnt-5a protein expression is frequently lost in hepatocellular carcinoma; this supports the notion that this protein has a tumour suppressor function in hepatocellular carcinoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Cadherins / analysis
  • Carcinoma, Hepatocellular / chemistry*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Child
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Liver Neoplasms / chemistry*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins / genetics
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wnt Proteins / analysis*
  • Wnt Proteins / genetics
  • Wnt-5a Protein
  • beta Catenin / analysis


  • Biomarkers, Tumor
  • Cadherins
  • Ki-67 Antigen
  • Proto-Oncogene Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • beta Catenin