Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 2083
© 2007 American Society of Clinical Oncology

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Abstract

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

Massachusetts General Hospital, Boston, MA

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.

Abstract presentation from the 2007 ASCO Annual Meeting