Correlation between VEGF expression and MVD in sporadic and NF2-related schwannomas

Abstract

2083 Background: Neurofibromatosis 2 (NF2) is a tumor suppressor syndrome characterized by the presence of bilateral vestibular schwannomas (VS) and multiple meningiomas for which alternative treatments are desperately needed. Currently there are no well- tolerated agents that are clinically active. Previous groups have shown VEGF expression in small series of VS. In this study, we expand these findings and show a significant relationship between VEGF bound to the vascular endothelium and microvascular density (MVD) in NF2-related VS. This observation providing a strong rationale for the use of VEGF blockade in this patient population. Methods: Formalin-fixed, paraffin-embedded specimens were obtained from surgical resections of 22 patients with sporadic VS and from 21 patients with NF2 VS. Sections were stained with anti-VEGF polyclonal antibody and with anti-CD31 monoclonal antibody. Intensity of immunostaining of tumor cells for VEGF was scored in semi-quantitative fashion (0-none, +1-mild, +2-moderate, +3-strong); MVD was calculated by averaging the number of CD31-positive vessels in 5–15 high -powered fields (20x). MVD in tumors with and without VEGF bound to the vascular endothelium were compared using t-test. Results: Expression of VEGF was detected in all sporadic and NF2 VS. Strong expression of VEGF in tumor cells was more common in sporadic VS (45%) than in NF2-related VS (5%). In contrast, endothelial-bound VEGF was more common in NF2- related VS (75%) than in sporadic VS (45%). There was no difference in mean MVD between sporadic (6.2%) and NF2-related tumors (6.1%). However, in NF2-related VS, MVD was significantly greater in tumors with endothelial bound VEGF (7.4%) than without (4.6%) (p < 0.05). Conclusions: VEGF expression in tumor cells was universal in this series of sporadic and NF2-related VS. Although the intensity of VEGF expression appears greater in sporadic tumors, endothelial- bound VEGF is more common in NF2-related lesions and is associated with greater MVD. This finding indicates a potential activity of the VEGF angiogenic pathway in this patient population. Therefore anti-VEGF therapy, such as bevacizumab, sunitinib, or sorafinib, represents a rationale approach to treating NF2 patients with VS in which surgical approach is not possible or has failed. No significant financial relationships to disclose.