Abstract
BackgroundHeparanase 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.ResultsHeparanase 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 MethodsParaffin 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).ConclusionHeparanase 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.
Highlights
Heparanase is the only mammalian endoglycosidase capable of cleaving heparan sulfate (HS) side chains of proteoglycans
For the entire cohort of metastatic melanoma patients, no apparent correlation was found between heparanase staining intensity and survival
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 1.14.1, p=0.025]
Summary
Heparanase is the only mammalian endoglycosidase capable of cleaving heparan sulfate (HS) side chains of proteoglycans. This activity is responsible for remodeling of the extracellular matrix (ECM) underlying epithelial and endothelial cells and is highly implicated in cellular invasion associated with angiogenesis, inflammation and metastasis [1, 2]. Heparanase expression is increased in many types of tumors and this elevation is frequently associated with more aggressive disease and poor prognosis, most often due to increased tumor metastasis [3,4,5]. Heparanase expression is induced in many types of cancers, including melanoma, and promotes tumor growth, angiogenesis and metastasis. There is insufficient data regarding heparanase expression in the metastatic lesions that are the prime target for anti-cancer therapeutics. We examined heparanase expression in metastatic melanoma and its correlation with clinical parameters
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