420P - Impact of Tumor Microenvironment on the Expression of Vascular Endothelial Growth Factor Receptor 2 in Glioblastoma Multiforme

Abstract

ABSTRACT Aim: The aim of our study was to evaluate the impact of tumor microenvironment (visual inflammation, inflammatory ICAM-1 expression) on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). Methods: Surgically excised GBM tissues (n = 42) were histologically examined for the overall extent of inflammation (score 1-3, based on typical appearance of inflammation, including presence of edema and inflammatory cell infiltration). After immunohistochemical staining procedure, tissue expression of ICAM-1 (optical density using pixel analysis software) as well as the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field) and endothelial staining intensity of VEGFR-2 (score 0-3) were determined. Results: In individual GBM samples, the extent of inflammation varied, being in the whole group 1.9 ± 0.7 (mean ± SD). Mean optical density of ICAM-1 (one of the mediators of inflammation) was 57,0 ± 27.1 (mean ± SD). The number of VEGFR-2+ blood vessels per microscopic field and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 (mean ± SD) and 1.2 ± 0.8 (mean ± SD) respectively. A positive association was found between VEGFR-2 staining intensity and the extent of inflammation (p = 0.005). Moreover, VEGFR-2 staining intensity correlated with the expression level of tissue ICAM-1 (p = 0.026). Conclusions: The expression of VEGFR-2 – one of the targets of anti-angiogenic therapy – depends on GBM microenvironment. Importantly, higher VEGFR-2 levels were seen in the presence of more pronounced inflammation, whereas in less inflamed tissues only weak expression of VEGFR-2 was found. Later has to be taken into consideration when VEGFR-2 targeting anti-angiogenetic drugs are tested in the treatment of GBM. This work was supported by grant IUT2-4. Disclosure: All authors have declared no conflicts of interest.