VEGF in the Development of Ovarian Malignancy

BackgroundIt is well known that the vascular endothelial growth factor (VEGF) system is essential to the growth of tumors, but its possible changes during tumor development are still sparsely elucidated. The current study, therefore, investigated the possible differences of VEGF and VEGFR-1 and VEGFR-2 protein concentration in tissue from patient groups with normal ovaries and those with benign, borderline, and malignant ovarian tumors. Furthermore, we investigated VEGF gene expression of the same groups.Material and MethodsWe analyzed tissue samples from 157 patients undergoing surgery of the ovaries. Tissue VEGF and VEGFR-1 and VEGFR-2 were measured by enzyme-linked immunosorbent assay, and gene expression was analyzed by reverse transcriptase polymerase chain reaction regarding VEGF isotypes 121, 165, and 189.ResultsSignificantly higher VEGF protein concentration was found in malignant tissue compared with normal ovarian tissue (P < 10-6) and benign ovarian tumors (P < 10-6). Similar results were found with respect to VEGFR-1. The gene expression differed among normal ovaries, benign, and malignant tumors for all Three VEGF isotypes (P < 10-6), with significantly higher levels of VEGF mRNA in malignant tumors. Malignant tumors with VEGFR-2 protein levels above the median had decreased progression-free survival (PFS) (P = .0005) and overall survival (P = .002). Median PFS was 26.2 months in the group with low VEGFR-2 levels vs. 7.8 months in the other group. Multivariate analysis confirmed the results (hazard ratio, 1.94; P = .04).ConclusionThe current study showed major changes in the VEGF system during tumor development. A significant difference was found in protein concentration and gene expression among the different patient groups. In addition, VEGFR-2 was correlated with PFS and overall survival.