Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., Canada.
Oncology. 2011;81(2):126-34. doi: 10.1159/000332849. Epub 2011 Oct 6.
Bevacizumab has promising activity against glioma, although reasons for poor efficacy and variable response rates in certain patients are unclear. Vascular endothelial growth factor receptor 2 (VEGFR2) is heterogeneously expressed within the microvasculature of various malignancies. Moreover, transforming growth factor β (TGF-β), a negative prognostic factor for glioma, is intimately involved in angiogenesis including VEGFR2 regulation. Our objective was to associate expression of VEGFR2 and TGF-β activity with clinicopathological features of human glioma.
Expression patterns determined by immunohistochemistry for VEGFR2 and phosphorylated Smad2 in human gliomas were compared to overall survival, progression-free survival (PFS), initial versus recurrent tumors and tumor grade.
Endothelial VEGFR2 expression was low or undetectable in normal tissue but the proportion of VEGFR2-positive vessels increased with tumor grade. Decreased PFS was associated with tumors whose vessels had increased proportions of VEGFR2 at recurrence. Neither parenchymal nor endothelial cell p-Smad2 was associated with tumor grade; however, the former was negatively correlated with overall survival in glioblastoma multiforme.
The molecular phenotype of the vasculature based on the status of VEGFR2 but not p-Smad2 is related to aspects of glioma progression and patient response. Changes in VEGFR2-positive vessels may account for variable therapeutic efficacy of anti-angiogenic agents.
贝伐单抗对神经胶质瘤具有良好的治疗作用，但在某些患者中疗效不佳和反应率存在差异的原因尚不清楚。血管内皮生长因子受体 2（VEGFR2）在多种恶性肿瘤的微血管中呈异质性表达。此外，转化生长因子β（TGF-β）是神经胶质瘤的一个预后不良因素，与血管生成有关，包括 VEGFR2 的调节。我们的目的是将 VEGFR2 的表达和 TGF-β活性与人类神经胶质瘤的临床病理特征联系起来。
通过免疫组织化学方法检测人类神经胶质瘤中 VEGFR2 和磷酸化 Smad2 的表达模式，并与总生存、无进展生存（PFS）、初发与复发肿瘤以及肿瘤分级进行比较。
正常组织中内皮 VEGFR2 表达低或无法检测，但随着肿瘤分级的增加，VEGFR2 阳性血管的比例增加。PFS 降低与复发时血管中 VEGFR2 比例增加的肿瘤有关。无论是实质细胞还是内皮细胞的 p-Smad2 均与肿瘤分级无关；然而，在多形性胶质母细胞瘤中，前者与总生存呈负相关。
基于 VEGFR2 状态而不是 p-Smad2 的血管分子表型与神经胶质瘤进展和患者反应有关。VEGFR2 阳性血管的变化可能是抗血管生成药物治疗效果存在差异的原因。
