Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer

J Pathol. 2002 Mar;196(3):292-9. doi: 10.1002/path.1051.


The calcium-binding protein S100A4 induces the metastatic phenotype in rodent models of breast cancer and its expression correlates strongly with reduced survival in human breast cancer. The expression of S100A4 in normal bladders and 101 bladder tumours has been studied using immunocytochemistry. Moderate or strong expression of S100A4 was found in 28% of the tumours, whilst the remaining tumours and normal urothelium either failed to stain or showed weak staining. S100A4 staining was more frequently observed in invasive bladder tumours than in non-invasive tumours (p<0.05). In invasive tumours, S100A4 staining was usually strongest in invasive regions and single infiltrating cells. Statistically significant associations were found between S100A4 expression and metastasis (p=0.0003) and reduced survival (p<0.0001). It is concluded that S100A4 expression may play an important role in bladder cancer and may identify a subgroup of patients at increased risk of metastasis who should be considered for adjuvant systemic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology*
  • Carcinoma in Situ / therapy
  • Carcinoma, Papillary / mortality
  • Carcinoma, Papillary / pathology*
  • Carcinoma, Papillary / therapy
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Risk Factors
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / analysis*
  • Survival Rate
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / therapy


  • Biomarkers, Tumor
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100A4 protein, human