THE PROGNOSTIC VALUE OF VEGF-C, -D AND ITS COGNATE RECEPTORS IN GLIOBLASTOMA PATIENTS

Introduction: So far, only few studies have investigated the patterns of angiogenesis markers in human Glioblastoma (GBM), mostly focused on vascular endothelial growth factor type A (VEGF-A). Until recently, VEGF-C and -D were not researched targets due to their established primarily role in lymphangiogenesis, which were considered absent in CNS. Objective: to evaluate the expression of VEGF-A, -C, -D and its receptors, VEGFR-1, -2, and -3 and clinical data for potential relations with common clinicopathological features and outcomes, as well as to investigate the prognostic value of different VEGF family members. Methods: tumor tissue samples of 70 GBM patients were assessed by immunohistochemistry assay using tissue microarray construction for VEGF families and its cognate receptors. The medical records of those patients were reviewed to obtain relevant clinical and therapeutical data. Results: the VEGF-A immunoreactivity was observed in 57 (81.4%) tumor cells of GBM samples. VEGF-C was expressed in 53 (75.7%) and, VEGF-D was seen in 55 (78.6%). The frequency of immunoexpression of VEGFRs was as follow: VEGFR-1, 65 (92.9%); -2, 63 (90%); -3, 49 (70%). No expression of VEGF-C, -D, and VEGFR-2, -3 was observed in normal brain tissue. Overall, there were no significant differences in overall survival regardless the staining intensity on tumor cells. A weak and monotonous correlation pattern was observed between VEGF and its cognate receptors. Intermediate correlation was only found for VEGFA and VEGFR2 (Spearman = 0.478), as for VEGFD and VEGFR2 (Spearman = 0.456). Conclusion: there were no significant differences in OS regardless the immunostaining intensity of VEGF and its cognate receptors on tumor cells. The overexpression of the axis of VEGF-C, -D, VEGFR-2 and -3 might be interpreted as an investigational target to clarify that theory, especially given the recent data that suggests that there is a complex lymphatic system in CNS and its development and modeling may be closed related to the interactions between VEGF-C and VEGFR-3. Further studies are needed to ascertain the increasing role of VEGF-C, – D and its receptors VEGFR-2 and -3 in GBM patients.