Expression of hypoxia-inducible factor-1α in oligodendrogliomas

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Abstract
Hypoxia-inducible factor (HIF)1α is considered to play a key role in the adaptation of cells to hypoxia by stimulating angiogenesis via regulation of vascular endothelial growth factor and by metabolic adaptation to O2 deprivation. Expression of HIF-1α protein and p53 was investigated by immunohistochemistry in 51 specimens of supratentorial pure oligodendrogliomas. Microvessels density (MVD) was determined by anti-CD34 immunostaining. The influence of HIF-1α expression on survival was investigated using univariate and multivariate analysis. Strong expression of HIF-1α was observed in 12 (23.5%) specimens, moderate in 21 (41.2%) specimens, and weak in 8 (15.7%) cases, and no expression was found in 10 samples (19.6%). There was no correlation of HIF-1α expression with histologic grading (P = 0.428, Mann–Whitney test). Hypoxia-inducible factor–1α expression and MVD showed a strong correlation (P < 0.001, r = 0.735, Spearman coefficient of correlation). Overexpression of p53 was observed in only two cases. Patients with strong or moderate expression of HIF-1α had a significantly shorter overall survival rate compared with those with low or no expression in univariate (P = 0.0434; log-rank test) and multivariate analysis (P = 0.0187). Overexpression of HIF-1α indicates a diminished prognosis in oligodendrogliomas, independent of p53 status. This finding may be explained by the strong vascularization of these tumors that prevents hypoxia and allows O2 diffusion and henceforth tumor progression. Cancer 2001;92:165–171. © 2001 American Cancer Society.