ANGI-08. DECODING VEGF SIGNALLING LANDSCAPES IN VARIOUS GLIOBLASTOMA TUMOUR MICROENVIRONMENTS

Abstract BACKGROUND Glioblastoma is a highly vascular and angiogenic tumour, yet its vasculature is structurally and functionally heterogeneous across different tumour microenvironments (TME). While the role of abnormal vessel formation in tumour progression is well established, the functional diversity of tumour vessels remains poorly characterised. To address this, we examined structural and functional vascular features, including spatial patterns of VEGF ligand and receptor expression. METHODS Formalin-fixed, paraffin-embedded tissues from 40 glioblastoma cases were labelled with a vascular antibody panel (PDGFRβ, ColIV, αSMA, UEA-1) to identify vessel subtypes. Additional staining for VEGFa, VEGFR1, and VEGFR2 was conducted in 11 GBM cases spanning key tumour microenvironments. This was done to assess the spatial expression of angiogenic signalling components. Tumour tissue was segmented into tumour core (TC), infiltrating tumour (IT), and leading edge (LE) to assess regional variation. RESULTS We identified different vessel subtypes across different TMEs, including previously described microvascular proliferation and hyperplastic blood vessels, but also classified novel subtypes, including ghost vessels and hybrid vessels. In assessing the expression of the VEGF family, we found that rather than being associated with specific vessel subtypes, the pattern of VEGFa ligand and VEGFR1/2 expression was more prominently associated with different TMEs, particularly areas of necrosis/hypoxia. CONCLUSION Spatially distinct VEGF/VEGFR expression in glioblastoma suggests that functional angiogenic signalling varies across tumour regions, highlighting the importance of microenvironment-specific profiling. Targeting angiogenic pathways in a regionally tailored manner may offer new strategies for improving vascular normalisation and therapeutic delivery in glioblastoma.