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


CONCLUSIONS
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.
Hashimoto
Yosuke
Y
Dept. of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. yo.hashimoto@scchr.jp
Skacel
Marek
M
Adams
Josephine C
JC
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008840:Microfilament Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism; D053668:Syndecan-1 / Q000096:biosynthesis* / Q000172:deficiency
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008840:Microfilament Proteins; C508241:SDC1 protein, human; D053668:Syndecan-1; C020324:fascin