脑膜瘤组织VEGF/VPF、KDR的表达及意义

The Expressions of VEGF/VPF and KDR in Patients with Meningiomas and Their Clinical Implications

目的 研究脑膜瘤血管生成及瘤周脑水肿与VEGF/VPF及其受体KDR的关系。方法 采用Northern印迹分子杂交和免疫组化技术检测47例脑膜瘤组织VEGF/VPF mRNA、VEGF/VPF和KDR蛋白表达,分析其与微血管密度(MVD)和瘤周脑水肿度(DPTBE)的关系。结果 47例脑膜瘤均表达4.2Kb的VEGF/VPF mRNA片段,VEGF/VPF蛋白表达与其mRNA的表达一致,80.9％的肿瘤KDR蛋白表达阳性,VEGF/VPF和KDR分别定位于脑膜瘤瘤细胞和血管内皮细胞胞浆。VEGF/VPFmRNA表达与脑膜瘤MVD和DPTBE呈正相关(r=0.67,P<0.01;r=0.54,P<0.01);KDR阳性组脑膜瘤VEGF/VPF mRNA表达水平、MVD、DPTBE均显著高于KDR阴性组(P<0.01)。结论 脑膜瘤细胞可产生VEGF/VPF,通过KDR介导促肿瘤血管生成和增加血管通透性,在脑膜瘤瘤周脑水肿的发生发展过程中起重要作用。

Objective To investigate the relationship among angiogenesis, degree of peritumoral brain edema (DPTBE), and vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and its receptor KDR in the patients with meningiomas. Methods Using the Northern Blot analysis and immunochemistry techniques, the extent of expressions of VEGF mRNA, VEGF/VPF and KDR was assessed and the relationship among them and the microvascular density (MVD) and DPTBE was observed in 47 patients with meningiomas. Results Tumors tissues of all the 47 cases expressed 4.2 Kb transcripts of VEGF/VPF mRNA. The expression of VEGF/VPF protein was in consonance with that of its mRNA. Positive KDR expression was seen in 80.9% of the tumors. VEGF/VPF and KDR were situated respectively in the tumors cells and vascular endothelial cells cytoplasm. The expression of VEGF/VPF mRNA was positively related with the extent of MVD and DPTBE (P<0.01 and P<0.05, respectively). In the patients with positive KDR expression, the VEGF/VPF mRNA, MVD and DPTBE were significantly higher than that in the patients with negative KDR (P<0.01). Conclusions These data suggest that VEGF/VPF delivered by meningioma cells may play an important role in the formation of peritumoral brain edema mediated by KDR, leading to increased angiogenesis and enhanced vascular permeability.