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Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms

Abu-Jawdeh, G.M.; Faix, J.D.; Niloff, J.; Tognazzi, K.; Manseau, E.; Dvorak, H.F.; Brown, L.F.

Laboratory Investigation; A Journal of Technical Methods and Pathology 74(6): 1105-1115

1996

ISSN/ISBN: 0023-6837
PMID: 8667614
Document Number: 469141
Angiogenesis is a critical factor in the growth, progression, and metastatic spread of solid tumors. Furthermore, angiogenesis has been correlated with prognosis in patients with ovarian cancer. The pathogenesis of the angiogenic events in ovarian cancer, however, are not well defined. Vascular permeability factor/vascular endothelial growth factor (VPF/NEGF) 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/NEGF and its receptors flt-1 and KDR in ovarian tumors. Four specimens of normal ovarian cortex and 41 specimens of benign (4), borderline (8), and malignant (29) ovarian tumors were studied by in situ hybridization, and in some cases by immunohistochemical analysis. VPF/NEGF 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/NEGF mRNA and protein were expressed by the neoplastic cells in all of the malignant tumors evaluated, with the majority of tumors (28 of 29) showing strong expression of mRNA. Serous borderline tumors had variable VPF/NEGF mRNA expression, with two of six cases showing focal strong expression and four showing low-level expression. No definite expression of VPF/NEGF was seen in two cases of mucinous borderline tumors. No strong expression of VPF/NEGF 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 malignant (60, 440 pM) and two borderline tumors (210, 590 pM) than in the seven benign serous cysts (mean, 10 +- 3 pM). In addition, microvascular endothelial cells strongly expressed mRNA of the VPF/NEGF receptors flt-1 and KDR and immunostained for VPF/NEGF protein in the majority of malignant and borderline tumors examined. These findings suggest that VPF/NEGF plays an important role in the angiogenesis associated with ovarian neoplasms.

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