title: Expression of hypoxia-inducible factor-1alpha and its relationship to tumour angiogenesis and cell proliferation in cartilage tumours.
abstract: We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1alpha, HIF-2alpha, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour. There was no HIF-1alpha and HIF-2alpha staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1alpha and HIF-2alpha expression was 40% and 25%, respectively. The tumour size (> or = 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1alpha expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1alpha and the MVD and a strong trend towards a correlation between HIF-1alpha and the PCNA index or histological grade. Our findings suggest that HIF-1alpha protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation.
authors.affiliation: Department of Orthopaedic Surgery, Hiroshima University, Hiroshima, Japan. kubot@hiroshima-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: T
authors.initials: T
authors.lastname: Sugita
authors.forename: S
authors.initials: S
authors.lastname: Shimose
authors.forename: T
authors.initials: T
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Arihiro
authors.forename: M
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation; D002813:Chondrosarcoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009372:Neoplasms, Connective Tissue / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016019:Survival Analysis; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018809:Proliferating Cell Nuclear Antigen; D000099162:Endothelial PAS Domain-Containing Protein 1