Heparanase is overexpressed in lung cancer and correlates inversely with patient survival

Cancer. 2008 Sep 1;113(5):1004-11. doi: 10.1002/cncr.23680.


Background: Heparanase is an endo-beta-D-glucuronidase that is capable of cleaving heparan sulfate (HS) side chains at a limited number of sites, yielding HS fragments of still appreciable size (approximately 5-7 kDa). Heparanase activity has been detected frequently in several cell types and tissues. Heparanase activity correlates with the metastatic potential of tumor-derived cells, a correlation that has been attributed to enhanced cell dissemination as a consequence of HS cleavage and remodeling of the extracellular matrix barrier.

Methods: In this study, the authors examined heparanase expression in 114 patients with lung cancer by means of immunohistochemistry and correlated clinical-pathologic data with heparanase immunostaining and cellular localization.

Results: Heparanase was overexpressed in 75% of the study patients. Heparanase expression was correlated with lung cancer lymph node status and metastasis classification (P = .04 and P = .01, respectively) and was correlated inversely with patient survival (P = .007). It is noteworthy that this adverse effect depended largely on the cellular localization of heparanase. Thus, whereas cytoplasmic staining of heparanase is associated with a poor prognosis, nuclear heparanase predicts a favorable outcome for patients with lung cancer.

Conclusions: The current findings suggest that heparanase expression and cellular localization are decisive for lung cancer patients' prognosis, most likely because of heparanase-mediated tumor cell dissemination by blood and lymph vessels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Aged
  • Biomarkers, Tumor
  • Cell Nucleus / enzymology
  • Cytoplasm / enzymology
  • Female
  • Glucuronidase / metabolism*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / enzymology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Survival Rate


  • Biomarkers, Tumor
  • heparanase
  • Glucuronidase