The Relationships Among The Expressions Of HIF-1α And VEGF In Gliomas And The Angiogenesis Of Glioma

Objective Glioma is the most frequent intracranial tumor,which has a bad prognosis, and its recurrence rate is high.Glioma is one of the most vascularized tumors of the human being.The growth and the invasion of glioma have a close relationship with the angiogenesis of the tumor.The angiogenetic mechanism of glioma includes:the growth of tumor results in hypoxia,which causes the up-expressions of several correlated cytokines.These cytokines have effects on vascular endothelial cells and extracellular matrix,they can promote neovascularization.The expressions of HIF-1αand VEGF and microvascular density(MVD) in 11 normal brain tissues and 57 gliomas were investigated, to analyse the relationships among them and discuss the possibility of taking HIF-1αand VEGF as the anti-angiogenetic targets.Method 57 paraffin imbeded samples of glioma tissues were gathered.After common section and HE staining,all these samples were pathological graded with the grading standards of WHO 1999.Each sample was cut into three sections,the three sections were immunohistologychemical stained with HIF-1α,VEGF and factorⅧrelated antigen. The factorⅧrelated antigen labelled tumor vessels were microscopic calculated to get the microvascular density(MVD).The expressions of HIF-1αand VEGF in normal brain tissues and gliomas were observed with microscope.The relationships among the expressions of HIF-1αand VEGF in gliomas and the angiogenesis of glioma were analysed.Results None of the 11 normal brain tissues expressed HIF-1α, HIF-1αexpressions were detected in 57 gliomas with a 40.35% positive rate.The expression rate of HIF-1αin gliomas was higher than the normal brain tissues(χ2 =5.026,P=0.012); HIF-1αexpressions were detected in 30 lower grade gliomas(WHO gradeⅠ-Ⅱ) with a 26.70% positive rate,oppositely in 27 higher grad gliomas (WHO gradeⅢ-Ⅳ) with 55.60% positive rate.The expression rate of HIF-1αin higher grade gliomas was higher than lower grade gliomas(χ2 =4.927,P=0.033);VEGF expressions were detected in 11 normal brain tissues with a 9.09% positive rate,oppositely in 57 gliomas with a 49.12% positive rate.The expression rate of VEGF in gliomas were higher than the normal brain tissues(χ2 =4.515,P=0.018); VEGF expressions were detected in 30 lower grade gliomas(WHO gradeⅠ-Ⅱ) with a 33.33% positive rate,oppositely in 27 higher grad gliomas (WHO gradeⅢ-Ⅳ) with 66.67% positive rate.The expression rate of VEGF in higher grade gliomas was higher than lower grade gliomas(χ2 =6.318,P=0.017); The microvascular density of normal brain tissues was 12.98,the microvascular density of lower grad gliomas was 22.67, the microvascular density of higher grad gliomas was 30.69, the microvascular density of lower grad gliomas was higher than normal brain tissues and the microvascular density of higher grad gliomas was higher than the lower grad gliomas(P<0.05).HIF-1αand VEGF coexpressed in glioma(χ2 =7.239,P=0.01);The microvascular density of 23 HIF-1αexpressed tissues was 37.76,the microvascular density of 45 HIF-1αunexpressed tissues was 17.40, the microvascular density of 23 HIF-1αexpressed tissues was higher than 45 HIF-1αunexpressed tissues(t=9.201,P<0.01).The microvascular density of 29 VEGF expressed tissues was 33.85,the microvascular density of 39 VEGF unexpressed tissues was 17.18, the microvascular density of 29 VEGF expressed tissues was higher than 39 VEGF unexpressed tissues(t=6.80,P<0.01).Conclusions The expressions of HIF-1αand VEGF in gliomas is positively related with the pathological grading of gliomas. HIF-1αand VEGF play a important role in the angiogenesis of glioma. HIF-1 is the key transcription factor of glioma in hypoxia,it can promote the transcription of several bioactive molecules,VEGF inclusive.VEGF have effect on vascular endothelial cells and promote cell proliferation and migrate,so that it can induce canalization of vascular endothelial cells.because of the key role of HIF-1αand VEGF in angiogenesis,they can be choosed as targets of antiangiogenic therapy.