VEGF, flt-1, and KDR/flk-1 as prognostic indicators in endometrial carcinoma

Objective. Tumor angiogenesis is a highly regulated process under the influ ence of the host microenvironment and mediators. Studies of breast cancer a nd, more recently, ovarian and cervical cancer, demonstrate that neovascula rization correlates with the likelihood of metastasis and recurrence. Vascu lar endothelial growth factor (VEGF), an important regulator of tumor angio genesis in the endometrium, flt-1, and KDR/flk-1 are good markers of vascul ar proliferation. Being that angiogenesis is a precursor to the development of progressive disease, we hypothesize that quantifying VEGF, flt-1, and K DR/flk-1 expression in uterine malignancies is a superior predictor of meta static potential and survival than is FIGO grade of tumor, depth of invasio n, and histology. Methods. The histologic slides of 47 patients with uterine malignancies (35 adenocarcinomas, 6 papillary serous, and 6 carcinosarcomas) were reviewed. The paraffin blocks from the primary tumor were obtained. Immunohistochemi stry staining was performed for VEGF, flt-1, and KDR/flk-1. Microvessel den sity, used to analyze VEGF and receptor concentrations, was determined by t wo independent investigators, who were blinded to the patients clinical sta tus. The impact of VEGF, flt-1, and KDR/flk-1 as well as stage, grade, dept h of invasion, and nodal status on the incidence of metastases, recurrence, and survival was determined using logistic regression analysis and product limit life system survival analysis, respectively. Results. Results indicated that when evaluating all three histologic types, only stage and grade of tumor were found to impact upon the incidence of r ecurrence and survival. When patients with carcinosarcoma and papillary ser ous adenocarcinoma were excluded from the analysis, once again only stage a nd grade of tumor were significant prognostic indicators of recurrence and survival. Only grade of tumor and depth of uterine invasion were significan t predictors of a tumor's metastatic potential. VEGF, flt-1, and KDR/flk-1 proved to be of little significance in predicting metastases, recurrence, a nd survival. Patients with advanced disease in all three histologic subtype s often had low VEGF and receptor positivity. Conclusions. In this study, VEGF, flt-1, and KDR/flk-1 receptor concentrati ons did not correlate with the incidence of metastases, recurrence, and sur vival. (C) 2000 Academic Press.