Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: an immunohistochemical study of clinically annotated tumors

BMC Cancer. 2008 Jun 30;8:185. doi: 10.1186/1471-2407-8-185.

Abstract

Background: Syndecan-1 is a transmembrane proteoglycan with important roles in cell-cell and cell-extracellular matrix adhesion and as a growth factor co-receptor. Syndecan-1 is highly expressed by normal epithelial cells and loss of expression has been associated with epithelial-mesenchymal transition and the transformed phenotype. Loss of epithelial syndecan-1 has been reported in human colorectal adenocarcinomas, but whether this has prognostic significance remains undecided. Here we have examined syndecan-1 expression and its potential prognostic value with reference to a clinically annotated tissue microarray for human colon adenocarcinomas.

Methods: Syndecan-1 expression was examined by immunohistochemistry of a tissue microarray containing cores from 158 colorectal adenocarcinomas and 15 adenomas linked to a Cleveland Clinic, IRB-approved database with a mean clinical follow-up of 38 months. The Kaplan-Meier method was used to analyze the relationship between syndecan-1 expression and patient survival. Potential correlations between syndecan-1 expression and the candidate prognostic biomarker fascin were examined.

Results: Syndecan-1 is expressed at the basolateral borders of normal colonic epithelial cells. On adenocarcinoma cells, syndecan-1 was present around cell membranes and in cytoplasm. In 87% of adenocarcinomas, syndecan-1 was decreased or absent; only 13% of patients had stained for syndecan-1 on more than 75% of tumor cells. Decreased syndecan-1 correlated with a higher TNM stage and lymph node metastasis and was more common in males (p = 0.042), but was not associated with age, tumor location or Ki67 index. Reduced tumor syndecan-1 staining also correlated with upregulation of stromal fascin (p = 0.016). Stromal syndecan-1 was observed in 16.6% of tumors. There was no difference in survival between patients with low or high levels of either tumor or stromal syndecan-1.

Conclusion: Syndecan-1 immunoreactivity was decreased in the majority of human colon adenocarcinomas in correlation with TNM stage and metastasis to local lymph nodes. In a small fraction of adenocarcinomas, syndecan-1 was upregulated in the local stroma. Syndecan-1 expression status did not correlate with patient survival outcomes. Combined analysis of syndecan-1 in relation to a potential prognostic biomarker, fascin, identified that loss of tumor syndecan-1 correlated significantly with strong stromal fascin staining.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Carrier Proteins / biosynthesis
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microarray Analysis
  • Microfilament Proteins / biosynthesis
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Stromal Cells / metabolism
  • Syndecan-1 / biosynthesis*
  • Syndecan-1 / deficiency

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • Microfilament Proteins
  • SDC1 protein, human
  • Syndecan-1
  • fascin