The prognostic significance of heparanase expression in metastatic melanoma

// Olga Vornicova 1,* , Ilanit Boyango 2* , Sari Feld 2 , Inna Naroditsky 3 , Olga Kazarin 1 , Yaniv Zohar 3 , Yariv Tiram 2 , Neta Ilan 2 , Ofer Ben-Izhak 3 , Israel Vlodavsky 2 , Gil Bar-Sela 1 1 Division of Oncology, Rambam Health Care Campus, Haifa, Israel 2 Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel 3 Department of Pathology, Rambam Health Care Campus, Haifa, Israel * These authors have contributed equally to this study Correspondence to: Gil Bar-Sela, email: // Israel Vlodavsky, email: // Keywords : heparanase; heparanase 2; melanoma; metastasis; survival Received : September 20, 2016 Accepted : September 26, 2016 Published : October 06, 2016 Abstract Background. Heparanase expression is induced in many types of cancers, including melanoma, and promotes tumor growth, angiogenesis and metastasis. However, there is insufficient data regarding heparanase expression in the metastatic lesions that are the prime target for anti-cancer therapeutics. To that end, we examined heparanase expression in metastatic melanoma and its correlation with clinical parameters. Results. Heparanase staining was detected in 88% of the samples, and was strong in 46%. For the entire cohort of metastatic melanoma patients, no apparent correlation was found between heparanase staining intensity and survival. However, in a sub group of 46 patients diagnosed as stage IVc melanoma, strong heparanase staining was associated with reduced survival rates [hazard ratio=2.1; 95%CI 1.1-4.1, p =0.025]. Material and Methods. Paraffin sections from 69 metastatic melanomas were subjected to immunohistochemical analysis, applying anti-heparanase antibody. The clinical and pathological data, together with heparanase staining intensity, were evaluated in a logistic regression model for site of metastasis and survival. Slides were also stained for the heparanase-homolog, heparanase-2 (Hpa2). Conclusion. Heparanase is highly expressed in metastatic melanoma and predicts poor survival of stage IVc melanoma patients, justifying the development and implementation of heparanase inhibitors as anti-cancer therapeutics.