Heparanase expression in malignant salivary gland tumors inversely correlates with long-term survival.

BACKGROUND Upregulation of the endo-beta-D-glucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local and distant metastatic spread, increased vascular density, and reduced postoperative survival. PATIENTS AND METHODS We analyzed heparanase expression in 60 patients (aged 59 +/- 17 years) with malignant salivary tumors (39 males and 21 females) using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity. RESULTS Heparanase staining was positive (> 0) in 70% of tumors (42 of 60 patients) and was negative (0) in the remaining 30% (18 patients). The cumulative survival of patients diagnosed as heparanase-negative (n = 18) at 300 months was 70% (95% confidence interval = 35-88). In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42) at 300 months was 0% (statistically significant difference, P = .035). CONCLUSIONS Heparanase expression levels inversely correlate with the survival rates of salivary gland cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy and an attractive target for anticancer drug development.