Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis.
BACKGROUND
Hypoxia-inducible factor (HIF)1 alpha 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 O(2) deprivation.


METHODS
Expression of HIF-1 alpha 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-1 alpha expression on survival was investigated using univariate and multivariate analysis.


RESULTS
Strong expression of HIF-1 alpha 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-1 alpha expression with histologic grading (P = 0.428, Mann-Whitney test). Hypoxia-inducible factor-1 alpha 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-1 alpha 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).


CONCLUSIONS
Overexpression of HIF-1 alpha 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 O(2) diffusion and henceforth tumor progression.
Birner
P
P
Institute of Clinical Pathology, University of Vienna, Vienna, Austria.
Gatterbauer
B
B
Oberhuber
G
G
Schindl
M
M
Rössler
K
K
Prodinger
A
A
Budka
H
H
Hainfellner
J A
JA
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000502:physiology; D009837:Oligodendroglioma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D011379:Prognosis; D016019:Survival Analysis; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53