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

Abstract

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. 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. 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. 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.