Expression of Hypoxia Inducible Factor-1a Correlates with Microvessel Density in Glioblastoma Multiforme

Abstract
Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumour characterized by marked angiogenesis, invasiveness and poor outcome. Intratumoral hypoxia possibly plays a key role in GBM growth and angiogenesis. A key regulator of adaptive response to hypoxia is the hypoxia inducible factor 1-alpha (HIF-1a) protein.
Aim of Study: The present study aimed to evaluate the expression of HIF-1a  in tumour cells of GBM and analyze its relation to tumour microvessel density.
Material and Methods: Fifty formalin fixed paraffin embedded tissue blocks of GBM were studied immunohisto-chemically for HIF-1a  expression using anti-HIF-1a  mono-clonal antibody and for microvessel density using anti-CD34 monoclonal antibody.
Results: HIF-1a  expression was observed in 86% of the studied cases. The immuostaining scores were negative in 14%, weak positive in 20%, moderate positive in 28% and strong positive in 38% of cases The mean microvessel counts were 14.3±11.5 in the negative cases, 21.6±15.8 in the weak positive cases, 27.2±21.7 in the moderate positive cases and 32.8±16.3 in the strong positive cases. A statistically significant relation was found between the expression of HIF-1a  protein and microvessel density in the studied GBM cases (p=0.01).
Conclusion: Our findings have shown that expression of HIF-1a  protein is correlated to the microvessel density in GBM, supporting evidence that different types of tumours can induce aberrant angiogenesis through HIF-1a. Thus, an understanding of the relationship between HIF-1a  and tumour angiogenesis in GBM may provide further therapeutic oppor-tunities for patients with this tumour.