Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis

J Surg Oncol. 2004 Sep 15;87(4):174-81. doi: 10.1002/jso.20097.

Abstract

Background: Heparanase is considered to play an important role in tumor invasion and hematogenous metastasis. The aim of this study was to determine the expression of heparanase in colorectal cancer to evaluate its prognostic value.

Methods: We analyzed heparanase mRNA derived from 130 colorectal cancer patients by reverse transcription polymerase chain reaction (PCR), compared its expression with clinicopathologic factors, and performed statistical analysis. To investigate the relationship between heparanase expression and tumor angiogenesis, 81 primary colorectal tumors were immunostained by use of a monoclonal anti-CD34 antibody.

Results: Thirty three of 130 cancer tissues overexpressed heparanase. There were significant correlations between heparanase expression and serosal invasion, venous invasion, and liver metastasis. Multivariate analyzes revealed that heparanase mRNA overexpression was a significant independent risk factor for hematogenous metastasis in colorectal cancer. Among 104 patients who underwent curative resection, heparanase expression correlated with a high recurrence. The 5-year survival rate was 84.6% for patients with heparanase negative tumors, and 47.7% for those with heparanase overexpression; these differences between two groups of patients were significant. In multivariate analysis using the Cox regression model, heparanese expression emerged as an independent prognostic indicator. Moreover, the tumor angiogenesis of heparanase-positive tumors determined with a monoclonal anti-CD34 antibody was significantly higher than that of heparanase-negative tumors.

Conclusions: These results indicated that Heparanase expression may be an important role in invasion and hematogenous metastasis, and may be a biologic marker of prognostic significance in colorectal cancer patients.

MeSH terms

  • Cell Line, Tumor
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Glucuronidase / biosynthesis*
  • Glucuronidase / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • Liver Neoplasms / secondary
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplastic Cells, Circulating / metabolism*
  • Neovascularization, Pathologic / enzymology*
  • Peritoneal Neoplasms / epidemiology
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • RNA, Messenger
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • heparanase
  • Glucuronidase