Spatial expression of VEGF-A in human glioma.

Astrocytoma, especially of high grade, is dependent on neovascularization for its growth and progression. The expression of vascular endothelial growth factor (VEGF-A), an important angiogenesis factor, has been demonstrated in perinecrotic cells in glioblastoma. In order to achieve more knowledge regarding the process of astrocytoma angiogenesis and growth we have investigated the expression of VEGF-A immunohistochemically in different areas of tumors. In 21 patients with astrocytomas of varying grade serial stereotactic biopsies were performed. Biopsies were taken from brain adjacent to tumor (BAT), tumor periphery, and tumor center. In the BAT region of high-grade astrocytomas, we found a frequent expression of VEGF-A in tumor cells and less frequent in blood vessels. In the periphery, there was an expression mainly in tumor cells while in the center of grade IV tumors VEGF-A was also frequently expressed in cells adjacent to necrosis. VEGF-A in astrocytoma grade II was demonstrated in viable tumor cells preferentially in the periphery but also in peripheral vessels and in centrally located tumor cells. The findings indicate that, in addition to hypoxia in necrotic areas there may be other factors that stimulate the expression of VEGF-A. It is suggested that VEGF-A may be a prerequisite for the aggressive and infiltrative growth of astrocytomas. Therefore, when operating high-grade astrocytomas it may be of importance to resect this aggressive peripheral part of the tumor and also to take this finding into account when planning radiotherapy.