title: Heparanase localization and expression by head and neck cancer: correlation with tumor progression and patient survival.
abstract: Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS) side chains of HS proteoglycans, the major proteoglycans in the extracellular matrix and cell surfaces. Traditionally, heparanase activity was implicated in cellular invasion associated with angiogenesis, inflammation, and cancer metastasis. More recently, heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival rate and enhanced tumor angiogenesis. In the present study, we examined the expression of heparanase in squamous cell carcinoma of the head and neck by means of immunostaining, and we correlated expression levels with patient outcome. The intensity and extent of heparanase staining correlated with tumor stage (P = .049 and P = .027, respectively), and the extent of staining further correlated with tumor grade (P = .047). Moreover, heparanase expression inversely correlated with patient status at the end of the study (P = .012). Notably, heparanase localization was found to be an important parameter for patient status. Thus, 63% of patients with nuclear staining, compared to 19% of patients with cytoplasmic staining (P = .0043), were alive, indicating that nuclear localization of the enzyme predicts a favorable outcome.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Carmel Medical Center, Haifa, Israel. idoweck@netvision.net.il
authors.forename: Ilana
authors.initials: I
authors.lastname: Doweck
authors.forename: Victoria
authors.initials: V
authors.lastname: Kaplan-Cohen
authors.forename: Inna
authors.initials: I
authors.lastname: Naroditsky
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
mesh_terms: D002467:Cell Nucleus / Q000201:enzymology; D018450:Disease Progression; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007830:Larynx / Q000201:enzymology / Q000473:pathology; D009055:Mouth / Q000201:enzymology / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D010614:Pharynx / Q000201:enzymology / Q000473:pathology; D011237:Predictive Value of Tests; D015996:Survival Rate / Q000639:trends; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D009687:Nuclear Proteins; D000099175:Heparanase