Correlation of Delta-like ligand 4 (DLL4) with VEGF and HIF-1α expression in human glioma.

To investigate the potential role of the notch ligand delta-like ligand 4 (DLL4) in glioma angiogenesis, we examined whether its expression correlates with that of vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1α (HIF-1α). Eighty-two specimens of human glioma and 7 of normal brain tissue were subjected to immunohistochemical analysis for DLL4, VEGF and HIF-1α expression. Statistical analysis were performed to determine if protein expression correlated with clinicopathological parameters, including histological type, pathological grade, and microvessel density (MVD), determined using CD34-labelling. Expression of DLL4, VEGF and HIF-1α was very strong in gliomas, relative to normal tissues, linked with the malignant grade. Moreover, DLL4 staining positively correlated with VEGF and HIF-1α expression and with MVD. Thus our results indicate that DLL4 represents a potential biomarker and therapeutic target for glioma angiogenesis.