VEGFR2 expression and TGF-β signaling in initial and recurrent high-grade human glioma

Abstract

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.

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.

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.