Prognostic significance of vascular endothelial growth factor and its receptors in endometrial carcinoma

Objective. The aim of this study has been to evaluate the clinical signific ance of expression of VEGF and its receptors, Flt-1, KDR, and Flt-4, in end ometrial carcinomas. Methods. Specimens of endometrial carcinomas from 86 patients were investig ated immunohistochemically using respective specific antibodies. Additional ly, samples from 14 patients with complex atypical endometrial hyperplasia (AEH) and 15 patients with normal endometria were also examined. Immunohist ochemical assessment was classified as negative, weakly positive, and stron gly positive according to staining intensity and the percentage of positive cells. Results. In positive cases, VEGF and its receptors were usually expressed h omogeneously in the cytoplasms of cells in the endometrial carcimona, simil ar to the staining intensity of endothelial cells of stromal microvessels a djacent to carcinoma nests. The overall positive rates in the 86 carcinoma specimens were 66% for VEGF, 51% for Flt-1, 38% for KDR, and 57% for Flt-4. Their expressions in endometrial carcinoma tissues were high with signific ance or with borderline significance, compared to those in samples of compl ex AEH or normal endometria. Survival curves determined by the Kaplan-Meier method and univariate analysis showed VEGF, Flt-1, and Flt-4 overexpressio n to be related to poor prognosis of patients with endometrial carcinomas. However, multivariate analysis revealed that Flt-4 overexpression correlate d independently with poor survival, similar to a value for myometrial invas ion at one-half or more and that for retroperitoneal lymph node metastasis, whereas VEGF and Flt-1 overexpression did not. Conclusion. Flt-4 overexpression might he a promising prognostic indicator for survival of a patient with endometrial carcinoma. (C) 2000 Academic Pre ss.