title: The prognostic significance of heparanase expression in metastatic melanoma.
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].
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Vornicova
authors.affiliation: Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel.
authors.forename: Ilanit
authors.initials: I
authors.lastname: Boyango
authors.affiliation: Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Feld
authors.affiliation: Department of Pathology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Naroditsky
authors.affiliation: Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Kazarin
authors.affiliation: Department of Pathology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Zohar
authors.affiliation: Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel.
authors.forename: Yariv
authors.initials: Y
authors.lastname: Tiram
authors.affiliation: Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
authors.affiliation: Department of Pathology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Ben-Izhak
authors.affiliation: Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.affiliation: Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Bar-Sela
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D015870:Gene Expression; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D000099175:Heparanase
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000099175:Heparanase
keywords: heparanase; heparanase 2; melanoma; metastasis; survival