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The neurovascular unit (NVU) is implicated in glioma tumourigenesis and treatment resistance but intertumoural heterogeneity is not well characterised. We evaluated the structure of the glioma NVU across tumour grades, in primary and recurrent disease. We determined association to overall survival. Method Ethics approval was obtained (15/ES/0094). A tissue microarray was constructed using biopsies from 137 patients and was immunostained for endothelial cells (CD31), extracellular matrix (collagen-IV), pericytes (PDGFR-β and α-SMA) and tight junctions (claudin-V). The immunostaining was assessed using QuPath software and compared by one-way analysis of variance with Tukey post-hoc testing. Association to overall survival was by univariate Cox regression with hazard ratios (HR). Result Primary grade IV tumours had greater CD31+ than grade II tumours (P = 0.046) or recurrent tumours (P = 0.013). After normalising to CD31+, collagen-IV+ was greater in recurrent tumours than in primary grade IV tumours (P = 0.013). PDGFR-β+ was greater in primary grade II tumours than in primary grade III tumours (P = 0.002), primary grade IV tumours (P &amp;lt; 0.001) or recurrent tumours (P &amp;lt; 0.001). Normalised α-SMA+ was greater in recurrent tumours than in primary grade IV tumours (P = 0.021). CD31 + (HR: 1.028, P = 0.004) and collagen-IV + (HR: 1.014, P = 0.008) were negative prognostic factors. After normalisation, PDGFR-β + (HR: 0.975, P = 0.004), α-SMA + (HR: 0.971, P = 0.020) and claudin-V + (HR: 0.994, P = 0.021) were positive prognostic factors. Conclusion Neurovascular remodeling is a feature of malignancy and recurrent tumours have altered neurovascular phenotypes. Markers for pericytes, extracellular matrix and tight junctions supplement classical grading features and predict tumour behavior. Take-home Message Neurovascular remodeling is a feature of malignancy and recurrent tumours have altered neurovascular phenotypes. Markers for pericytes, extracellular matrix and tight junctions supplement classical grading features and predict tumour behavior.

O26 Intertumoural heterogeneity in the structure of the neurovascular unit in glioma: a retrospective observational cohort study