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.