Angiogenesis and Growth of Vestibular Schwannomas: Expression of VEGF, VEGFR1, and Extracellular Matrix Factors MMP-2, MMP-9, and TIMP-1

Objectives/Hypothesis: Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. This study targets the angiogenic process in relation to growth of vestibular schwannomas by investigation of tumor expression of VEGF, VEGF-R1, MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored.

Methods: Thirty-four patients with a sporadic, noncystic, vestibular schwannoma were selected prospectively. Repeated, preoperative magnetic resonance imaging determined the tumor growth pattern. Following translabyrinthine resection, an enzyme-linked immunosorbent assay was used for determination of the VEGF, VEGFR1, MMP-2, MMP-9, and TIMP-1 concentration in tumor sample homogenates. Immunohistochemical labeling was performed in 12 randomly selected tumors.

Results: Immunolabeling localized VEGF and MMP-9 expression to the tumor cells, whereas MMP-2 and TIMP-1 was found interstitially. A significant correlation existed between the concentration of VEGF, VEGFR-1, and MMP-9 and the tumor growth rate. No correlations existed between any clinical parameter and MMP-2 or TIMP-1 expression.

Conclusions: Vestibular schwannomas express VEGF, VEGFR-1, MMP-2, MMP-9, and TIMP-1, and the tumor concentration of VEGF, VEGFR-1, and MMP-9 correlates with the tumor growth rate, but not with age, gender, symptom duration, or tumor size. We conclude that VEGF, VEGFR-1, and MMP-9 are likely to be directly involved in the growth of vestibular schwannomas.