Research article

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

Yosuke Hashimoto^{* 1,4} , Marek Skacel^{* 2,5} and Josephine C Adams^1,3

¹Dept. of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

²Dept. of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, 44195, USA

³Dept. of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, 44195, USA

⁴Current Address: Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun 411-8777, Shizuoka, Japan

⁵Current Address: Molecular Pathology Laboratory, Dahl-Chase Pathology Associates, 417 State Street (suite 540), Bangor, ME, 04401, USA

author email corresponding author email* Contributed equally

BMC Cancer 2008, 8:185doi:10.1186/1471-2407-8-185

Published:	30 June 2008

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.