Conclusions
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.
Methods
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.
Objective
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.
Results
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. Conclusions: 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.