STRONG EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) AND ITS RECEPTORS IN OVARIAN BORDERLINE AND MALIGNANT NEOPLASMS

Angiogenesis is a critical factor in the growth, progression, and meta static spread of solid tumors. Furthermore, angiogenesis has been corr elated with prognosis in patients with ovarian cancer. The pathogenesi s of the angiogenic events in ovarian cancer, however, are not well de fined. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a multifunctional cytokine that has been shown to be an important regulator of tumor angiogenesis. The purpose of the present study was to define the expression of VPF/VEGF and its receptors fit- 1 and KDR in ovarian tumors. Four specimens of normal ovarian cortex a nd 41 specimens of benign (4), borderline (8), and malignant (29) ovar ian tumors were studied by in situ hybridization, and in some cases by immunohistochemical analysis. VPF/VEGF protein was also determined by an immunofluorometric assay in cyst fluids obtained from 11 patients, including 7 benign, 2 borderline, and 2 malignant tumors. VPF/VEGF mR NA and protein were expressed by the neoplastic cells in all of the ma lignant tumors evaluated, with the majority of tumors (28 of 29) showi ng strong expression of mRNA. Serous borderline tumors had variable VP F/VEGF mRNA expression, with two of six cases showing focal strong exp ression and four showing low-level expression. No definite expression of VPF/VEGF was seen in two cases of mucinous borderline tumors. No st rong expression of VPF/VEGF mRNA was observed in normal ovarian cortex , including surface epithelium, or benign tumors. Substantially higher VPF protein concentrations were detected in cyst fluids of the two ma lignant (60, 440 pM) and two borderline tumors (210, 590 pM) than in t he seven benign serous cysts (mean, 10 +/- 3 pM). In addition, microva scular endothelial cells strongly expressed mRNA of the VPF/VEGF recep tors fit-1 and KDR and immunostained for VPF/VEGF protein in the major ity of malignant and borderline tumors examined. These findings sugges t that VPF/VEGF plays an important role in the angiogenesis associated with ovarian neoplasms.