Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma

Mod Pathol. 2002 Jun;15(6):593-8. doi: 10.1038/modpathol.3880571.


Previous reports have shown that the biochemical activity of heparanase is significantly correlated with the invasion and metastasis of malignant cells in vitro. Recently, it was found that the human heparanase gene was cloned and highly expressed in malignant cell lines and human solid malignant tumors. In the present study, we investigated the heparanase mRNA expression by using in situ hybridization in 116 paraffin-embedded tissues of primary gastric carcinomas. To explore its clinicopathologic significance, it was detected in the various steps of tumor progression and then compared with prognostic indicators. As a result, the heparanase expression was more prevalent in late-stage rather than early-stage carcinomas (P <.0001) and was more frequent in tumors of large size (P =.0212). Expression also correlated with lymphatic (P =.0086) and venous (P =.0171) invasion and with negative prognostic factors such as lymph nodal (P <.0001) and distant (P =.0221) metastases. However, in a multivariate analysis, messenger RNA expression of heparanase was not an independent prognostic factor. It was concluded that heparanase might play an important role in the development of invasion and metastasis of the gastric cancer. It was indicated that patients with heparanase-positive gastric carcinoma would have a greater chance of metastasis with a poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glucuronidase / genetics*
  • Humans
  • In Situ Hybridization
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Survival Analysis
  • Veins / pathology


  • RNA, Messenger
  • heparanase
  • Glucuronidase