Vascular Endothelial Growth Factar Expression In Human Glioma: Correlation With Peritumoral Vasogenic Brain Edema And Tumorassociated Cysts

Objective: Microvascular extravasation is a common accompaniment of systemic and central neural system (CNS) tumor. This process results in soft-tissue swelling, pulmonary edema, pleural effusions, ascites, peritumoral vasogenic brain edema (PVBE) , and brain tumor-associated cysts (TACs). The latter two epiphenomenas add considerably to brain tumor mass effect, contributing to both the local distortion of intracranial structures and a diffuse elevation of intracranial pressure, which would lead to series of clinic symptoms and signs.Many biochemical factors have been implicated in the genesis of brain edema. In recent years, a novel polypeptides has been found which is named vascular endothelial growth factor (VEGF). People have pay more and more attention to VEGF for its potent permeabitity effect and the ability to increase angiogenesis . Studies have shown that the VEGF molecule is approximately a 40-45 KD heparin-binding glycoprotein with two apparently identical chains held together by disulfide bonds. It appear to be a highly specificmitogen capable of inducing endothelial cell replacation and migration essential to angiogenesis. It can also increase the vascular permeability, and result in the extravasation of serum protein without the kesion of the vascular endothelial cell. It is also named as vascular permeability factor (VPF). The recently studies have shown that VEGF has a significant correlation to the tumor growth, invasion and metastasis. It has been a "hot spot" about VEGF in the role of the growth and development of human brain tumor and in the therapy study about anti-tumor angiogenesis. This investigation is undertaken to study patterns of VEGF protein expression in a serie of low grade and malignant gliomas to determine whether VEGF acts as a common pathophysiological link between two morphologically distinct epiphenomenas (PVBE and TACs) of microvascular extravasation are linked a pathophysiological mechanism involve VEGF, in hope of further clarifying the role of VEGF in neoplastic vasogenic brain edema, TACs and tumor grade. Methods:1. Protein expression of VEGF in 36 human gliomas and 8 normal brain tissues were examined by Streptavidin Peroxdase Conjugated immunohistochemical Method (SP), PBS taken for primary antibody was used as negative control, tumor cell in breast carcinomas was used as positive control.2. The number of vascular was measured by microvascular count (MVC) which was immunostained withanti-factor CD34 monoclonal antibody. It was measured at x200 field in microvessel "hot spot". Mivrovascular count was defined by averaging the number of vessels in five most vascular areas.3. Edema index (El) was used to evaluate the extent of PVBE by referring to a method by Goldman, which was a rate generated by dividing the edema volume by that of the tumor volume. Using the method, a result of 1.0 implied the absence of peritumal edema, whereas the presence of any edema would yield edema index, values treater than 1.0. The greater of El, the heavier of edema.4. The VEGF concentation of tumor cyst fluid and patient serum and control serum were measured by ELISA.5. Statistic Analysis: VEGF concentration, micro- vascular count edema index were expressed as the meansD. Statistically significant differences were determined by using Independent Sample T test. VEGF protein expression correlations with MVC and El were deterimined by Spearman Correlation.Results:1. Immunohistochemical stain for VEGF showed the distribution of VEGF was mainly in tumor cell of malignant gliomas, whereas it was weakly expressed in low grade gliomas, it was negative expressed in PVBE tussues and normal brain tissues. The expression rate in human gliomas was 77.8% (28/36).2. El in the malignant gliomas (3.83+2.55) was greater than that in low grade gliomas (1.67 + 0.72). there was a significant difference between them (t'=3.852 , p<0.01).3. CD34 monoclonal antibody were positive expressed in vascular endothelial cell membrane of normal brain...