Angiogenesis of glioma: evaluation of ultrastructural characteristics of microvessels and tubular bodies (Weibel?Palade) in endothelial cells and immunohistochemical findings with VEGF and p53 protein

Abstract

Capillary endothelial proliferation is often a prominent feature of malignant gliomas. The understanding of structural and functional characteristics of the vascular microenvironment in gliomas is essential for the design of future therapeutic strategies against this tumor. Electron microscopic analysis of the capillary endothelial proliferation in malignant gliomas indicated that the complex vascular structures within the tumor were composed essentially of immature capillaries. Immature capillaries had a narrow slitlike lumen composed of endothelial cells with their high nuclear : cytoplasmic ratio and the relative paucity of organelles. They resembled capillary buds seen in normal repair tissue. Immature microvessels caused by angiogenesis were found more frequently in marginal zone of the tumors with increased microvessels. The tubular body was an organelle observed in vascular endothelial cells and was used frequently as a marker of the endothelial cell. Tubular bodies were evaluated by quantitative measurement of the mean percent (%) ratio of the number of endothelial cells with tubular bodies to all endothelial cells in microvessels of tumors. In glioblastomas it yielded a value of 32.4% in the margin, about two times as high as that in the center of the tumors. However, it was lower in all locations of astrocytomas. Tubular bodies in endothelial cells could be increased in proportion to neovascularization, and they might serve as a marker for increasing microvessels in astrocytic tumors. Tumor angiogenesis may be regulated by growth factors with angiogenic activities that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation. We found that 86% of 29 glioblastomas and 79% of 14 anaplastic astrocytomas demonstrated immunoreactivity for VEGF in their tumor cells. There tended to be a correlation between VEGF and vascularity. A correlation existed between the grade of immunoreactivity for VEGF and the grade of p53 protein expression in the malignant gliomas. However, the MIB-1 indices did not increase in correlation with increase in the extent of immunoreactivity for VEGF.