Study On Expression Of HIF-1 And Correlation With Microvessel Density In Human Gliomas

BACKGROUND:Gliomas are the most common brain malignancy tumor.HIF-1α,which helps sustain the homeostasis of oxygen in the development of malignant tumors and metastasis,is considered to play a key role in the adaption of tumor cells to hypoxia.It is conceivedthat HIF-1αmay play a key role in the angiogenesis of gliomas.But there is not any report about the study on expression of HIF-1 and the correlation with microvessel density(MVD)in Human GliomasOBJECTIVE:To investigate the expressions of hypoxia induced HIF-1αprotein and HIF-1αmRNA in human gliomas and find out the correlation with glioma grades,microvessel density(MVD)and inwasiveness.METHODS:Fresh tissues of 36 patients with glioma and 10 normal brain tissues,including low malignance 21(gradeⅠ～Ⅱ)and high malignance 15(gradeⅢ～Ⅳ),were used in the present study.The expression of HIF-1αmRNA by these glioma tissues was examined by RT-PCR.Another 10 normal brain tissues and 45 cases of formalin-fixed, paraffin-embedded specimens of glioma,including low malignance 24 (gradeⅠ～Ⅱ)and high malignance 21(gradeⅢ～Ⅳ),were used to assess the expression status of HIF-1αprotein,FactorⅧand Ki-67 by immunohistochemical staining.The Ki-67 labeling index(LI)and microvessel density(MVD)were calculated.To analyze whether or not HIF-1αcould be used as an index of the malignancy and a predictor of poor prognostic for the patients with glioma,the correlation between HIF-1αexpression and the Ki-67 LI or the MVD was investigated.RESULTS:Positive expression of HIF-1αprotein rates was 62.2%in human glioma tissues and not detected in normal brain tissues.The positive rate was significantly higher in gliomas than in normal brain tissues(p＜0.05).Positive expression of HIF-1αprotein rates was 45.8%in pathologyⅠplusⅡtogether and 80.9%in pathologyⅢplusⅣtogether.HIF-1αprotein was more highly expressed in high glioma grades than in low grades.Expression of HIF-1αmRNA was not detected in normal brain tissues.HIF-1αmRNA positive expression rates was 57.1%in pathologyⅠplusⅡtogether and 93.3%in pathologyⅢplusⅣtogether.Expression of HIF-1αmRNA was significantly different between glioma and normal brain tissues.Expression of HIF-1αmRNA was significantly different between high glioma grades and low grades.HIF-1αprotein located in nucleus and plasm of glioma cells,and its expression correlated directly with Ki-67 and MVD (r=0.613,0.751,P＜0.01).Conclusions:HIF-1αis over expressed in gliomas,and there is a significant correlation with glioma grades.Expression of HIF-1αcorrelated directly with the degree of malignancy,Ki-67 and MVD in gliomas.It may play a key role in the rapid growth,invasion and angiogenesis of gliomas.