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

Eur J Gastroenterol Hepatol. 2008 Aug;20(8):756-65. doi: 10.1097/MEG.0b013e3282fc2649.


Aim: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Specificity
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Extracellular Matrix / metabolism*
  • Female
  • Glucuronidase / immunology
  • Glucuronidase / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism
  • Sensitivity and Specificity
  • Syndecan-1 / metabolism*
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • Neoplasm Proteins
  • SDC1 protein, human
  • Syndecan-1
  • heparanase
  • Glucuronidase