Increased ratio of vascular endothelial growth factor to semaphorin3A is a negative prognostic factor in human meningiomas

Semaphorin3A (SEMA3A) is an anti-angiogenic factor which is expressed in human meningiomas in association with low microvessel density (MVD). It competes with vascular endothelial growth factor (VEGF) for receptor neuropilin-1 (NRP-1). The ratio between VEGF and SEMA3A has been recently demonstrated to regulate neo-angiogenesis, proliferation and progression of tumors. To clarify the involvement of these proteins in the above-mentioned phenomena, we analyzed the immunohistochemical expression of SEMA3A, VEGF and NRP-1 and their correlation with MVD in a series of 48 cases of meningioma with different histotype and histological grade. SEMA3A and VEGF expression was encountered in about half the cases, although at different levels. NRP-1 staining was evidenced in the vessels within all but two tumors and in the neoplastic cells of 18/48 meningiomas. A negative significant correlation emerged between SEMA3A amount and MVD; on the other hand, high VEGF levels appeared to be significantly associated with high MVD. A high VEGF/SEMA3A was significantly associated with high histological grade, proliferation index and MVD as well as with a higher recurrence rate of the meningiomas. Present data suggest that the balance between the expression of the pro-angiogenic factor VEGF and the anti-angiogenic SEMA3A may be involved in the regulation of neo-angiogenesis and proliferation in meningiomas, representing also a predictor of recurrences in these tumors. Further validation of our results may open the way for the use of drugs targeting not only VEGF, but also NRP-1 and SEMA3A to prevent recurrences of meningiomas.