Heparanase Expression in Malignant Salivary Gl, 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.