Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma

To propose a quantitative method to detect heparanase-2 (HPA2) and syndecan-1 (Syn-1) using immunohistochemistry in colorectal (colon and rectal) carcinomas compared with nonneoplastic tissues and evaluate the possible role of these molecules in tumor development and extracellular remodeling.

Cytoplasmic staining of HPA2 and Syn-1 was obtained by standard immunohistochemical reactions in 50 colorectal carcinoma and 20 nonneoplastic large bowels tissues. An image system was used to quantify the immunoexpression by digital computer-assisted method (Matos et al. 2006). The cutoff point for the immunohistochemistry variable was defined by sensibility and specificity curves. Statistical analysis was performed using SPSS version 13.0.

HPA2 was over-expressed in colorectal cancer (131.1+/-24.9 o.u./microm) when compared with nonneoplastic tissues (27.9+/-12.2 o.u./microm) (P<0.0001). However, an opposite correlation was observed between Syn-1 and tumor presence, where colorectal tissues expressed lower Syn-1 proteoglycan compared with nonneoplastic tissues, respectively (39.2+/-17.8 o.u./microm) and (102.2+/-25.2 o.u./microm) (P<0.0001).

A methodology with high sensitivity and specificity is proposed with a cutoff value for HPA2 and Syn-1 in the immunohistochemistry assay to define the presence of tumor. It was demonstrated for the first time in the literature that HPA2 is over-expressed in colorectal carcinoma tissues compared with nonneoplastic tissues. HPA2 over-expression could be possibly related to Syn-1 shedding despite the fact that HPA2 does not present enzymatic activity as HPA1.