title: Heparanase expression in head and neck squamous cell carcinomas is associated with reduced proliferation and improved survival.
abstract: OBJECTIVE
  Cellular expression of heparanase, a degrading enzyme of the extracellular matrix, is associated with poorer prognosis in several cancers. The present analysis, has studied the role of heparanase in tumour growth and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC).
  
  
  RESULTS
  We analysed the cellular expression of the active form of heparanase in 71 human HNSCCs, using immunohistochemistry. The results were compared with clinicopathological data and, in 65 cases with immunoreactivity for the proliferation marker, MIB1. Cellular heparanase expression was detected in 41 of 71 (57.74%) cases; in particular, UICC IV-stage tumours showed high heparanase levels. Heparanase was localized mainly in the cytoplasm and, to a lesser extent, at the cell membrane. High levels of heparanase were significantly correlated with an almost four-fold decrease in MIB1 labelling (P = 0.006). Comparison with clinical outcome by multivariate analysis revealed that patients with high-level heparanase expression had prolonged overall survival (P = 0.029).
  
  
  CONCLUSIONS
  Although heparanase was mainly found in late-stage HNSCCs, cellular heparanase expression in HNSCCs was associated with prolonged overall survival. We propose that the proliferation-reducing effect of high heparanase levels might outweigh the tumour-promoting effects of heparanase, especially in advanced tumours.
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany. carolin.mogler@med.uni-heidelberg.de
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dyckhoff
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Jenetzky
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.forename: Burkhard M
authors.initials: BM
authors.lastname: Helmke
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D005966:Glucuronidase / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D005966:Glucuronidase; D019394:Ki-67 Antigen; D000099175:Heparanase