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• W879382017 abstract "4434 Vestibular schwannoma (VS) and meningiomas are benign tumors that comprise 35-40% of all brain tumors. Neurofibromatosis 2 (NF2) is characterized by the presence of bilateral VS and multiple meningiomas for which alternative treatments are desperately needed. Currently there are no agents that produce disease stabilization or regression. This lack of active drugs is especially critical for NF2 patients where tumor progression is common. Previous groups have shown VEGF expression in small series of sporadic VS. In this study, we expand these findings to include a larger sample VS that include both sporadic and NF2 tumors. We broadened our study to include 5 parameters commonly used to characterize angiogenesis in tumors: microvascular density (MVD), and immunolabeling for VEGF, VEGFR2, PDGFRalpha and PDGFRbeta. Formalin-fixed, paraffin-embedded specimens were obtained from surgical resections of 22 patients with sporadic VS and from 21 patients with NF2 that underwent surgical resection at MGH. Sections were stained with polyclonal antibodies against VEGF (Santa Cruz Biotechnology), VEGFR2, PDGFRalpha and PDGFRbeta; (Cell Signaling), CD31, and Factor VIII (Dako). Intensity of immunostaining was scored in semi-quantitative fashion (0: no expression, +1: mild expression, +2: moderate expression, +3: strong expression) for VEGF, VEGFR2 and PDGF Receptors. MVD was calculated by averaging the number of CD31-positive vessels in 5-15 fields (10x). Intensity of each parameter was quantified for endothelial and tumor cells respectively. Expression of VEGF was detected in all sporadic and NF2-related VS. Strong (+3) 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 (13.5 vessels/mm2) and NF2-related tumors (12.5 vessels/mm2). The number of vessels expressing VEGFR2 was greater in sporadic (10.7 vessels/mm2) than in NF2 (7.4 vessels/mm2). Similarly the percentage of tumors expressing PDGFRbeta on vessels was greater in sporadic tumors (82%) than in NF2 tumors (55%). 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 lesions, endothelial- bound VEGF is more common in NF2-related lesions and is positively associated with increased MVD. This finding indicates a potential activity of the VEGF angiogenic pathway in this patient population with subtle differences between NF2 and sporadic tumors with respect to the endothelial receptors. Therefore anti-VEGF therapy such as bevacizumab represents a rational approach to treating NF2 patients with VS in which surgery is not possible or has failed. A better understanding of the respective angiogenic mechanisms is necessary prior to using tyrosine kinase inhibitors." @default.
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• W879382017 date "2008-05-01" @default.
• W879382017 modified "2023-09-27" @default.
• W879382017 title "Angiogenesic profile in sporadic and NF2-related schwannomas" @default.
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