Vascular endothelial growth factor levels in ovarian cyst fluid correlate with malignancy

Ovarian cancer is a richly vascularized neoplasm with solid and cystic comp onents. The purpose of this study was to determine whether cyst fluid could be used to quantitatively evaluate production of angiogenic factors in ova rian lesions. ELISA was used to measure vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cyst fluid of patie nts with ovarian cancer (n = 13), benign cysts and cystadenomas (n = 23), b orderline tumors (n = 5), and functional cysts (n = 8), VEGF levels were ma rkedly elevated in the fluid of malignant cysts (38.5 +/- 8.2 ng/ml) as com pared with benign (1.6 +/- 0.4 ng/ml; P < 0.001), borderline (5.7 +/- 1.5 n g/ml; P < 0.001), or functional cysts (3.8 +/- 2.0 ng/ml; P < 0.001), The p resence of VEGF in cancer cells was confirmed by immunohistochemistry. Foll ow-up of patients with malignant and borderline lesions demonstrated a corr elation between VEGF levels in cyst fluid and tumor recurrence (P = 0.03), bFGF in malignant cysts was either undetectable or very low (0.3 +/- 0.2 ng /ml), and no significant differences were found in bFGF levels among malign ant, benign, borderline, and functional cysts. This study demonstrates that ovarian malignancy is associated with dramatic elevation of VEGF levels in ovarian cyst fluid. Conversely, there is no correlation between cyst fluid bFGF levels and malignant transformation. The high levels of VEGF in malig nant cysts are consistent with the hypothesis that this growth factor plays an important role in ovarian cancer related-angiogenesis and tumor progres sion and represents a potentially important target of antiangiogenic therap y.