Nuclear localization of the metastasis-related protein S100A4 correlates with tumour stage in colorectal cancer

J Pathol. 2003 Aug;200(5):589-95. doi: 10.1002/path.1381.


A large number of experimental studies have linked the S100A4 gene product to the metastatic phenotype of cancer cells and clinical evidence indicates a correlation between S100A4 expression and poor prognosis in several cancer types. The aim of the present study was to analyse the expression of the S100A4 protein in colorectal cancer. Paraffin-embedded samples from 277 colorectal cancer patients were immunostained with anti-S100A4 antibody. Cytoplasmic staining was observed in 178 of 277 samples (64%), whereas, unexpectedly, nuclear expression of S100A4 was found in 88 of 277 of the samples (32%). This novel finding was confirmed by western blot analysis of nuclear fractions isolated from frozen tumour tissue. Statistical analysis revealed a significant correlation between nuclear expression of S100A4 and tumour stage at diagnosis, while there was no such correlation between cytoplasmic staining and tumour stage. The nuclear localization of S100A4 in colorectal cancer and its relationship to tumour stage suggest that this protein may be involved in gene regulatory pathways of relevance to the metastatic phenotype of cancer cells.

Publication types

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

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cryopreservation
  • Cytoplasm / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Prospective Studies
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / metabolism*


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