Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas - Itsimpact on prognosis and on neoangiogenesis

BACKGROUND. Hypoxia-inducible factor (HIF)1 alpha is considered to play a k ey role in the adaptation of cells to hypoxia by stimulating angiogenesis v ia regulation of vascular endothelial growth factor and by metabolic adapta tion to O-2 deprivation. METHODS. Expression of HIF-1a protein and p53 was investigation by immunohi stochemistry in 51 specimens of supratentorial pure oligodendrogliomas. Mic rovessels density (MVD) was determined by anti-CD34 immunostaining. The inf luence of HIF-1 alpha expression on survival was investigated using univari ate and multivariate analysis. RESULTS. Strong expression of HIF-1 alpha was observed in 12 (23.5%) specim ens, 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 -1 alpha expression with histologic grading (P = 0.428, Mann-Whitney test). Hypoxia-inducible factor-la: expression and MVD showed a strong correlatio n (P < 0.001, r = 0.735, Spearman coefficient of correlation). Overexpressi on of p53 was observed in only two cases. Patients with strong or moderate expression of HIF-1<alpha> had a significantly shorter overall survival rat e compared with those with low or no expression in univariate (P = 0.0434; log-rank test) and multivariate analysis (P = 0.0187). CONCLUSIONS. Overexpression of HIF-1 alpha indicates a diminished prognosis in oligodendrogliomas, independent of p53 status. This finding may be expl ained by the strong vascularization of these tumors that prevents hypoxia a nd allows O-2 diffusion and henceforth tumor progression. Cancer 2001;92:16 5-171. (C) 2001 American Cancer Society.