Significance of tumour-associated macrophages, vascular endothelial growthfactor and thrombospondin-1 expression for tumour angiogenesis and prognosis in endometrial carcinomas

Angiogenesis is a key process in tumour growth and metastasis, and microves sel density has been found to influence the prognosis of endometrial carcin oma patients. Less is known about regulators of angiogenesis. Studies of ot her tumour types have indicated that the density of tumour-associated macro phages (TAMs) and the expression of vascular endothelial growth factor (VEG F) might stimulate vessel formation, whereas thrombospondin-1 (TSP-1) may i nhibit this process. We investigated the influence of TAM (CD68(+)), VEGF a nd TSP-1 expression on tumour vascular density and prognosis among endometr ial carcinoma patients and compared our findings with clinico-pathological variables and tumour markers, In a prospective study, 60 endometrial carcin oma patients with long (median 11 years) and complete follow-up were includ ed, Intratumour density of TAMs was significantly associated with FIGO stag e, histological type, histological grade, DNA index, estradiol receptor con centration, intratumour Ki-67 and p53 protein expression (all p < 0.05). Mo derate or strong expression of VEGF was significantly associated with serou s papillary/clear cell tumour types, high microvessel density and aneuploid y (p < 0.05). There was a tendency to strong TSP-1 expression among tumours with weak VEGF expression (p=0.09). TAM density influenced survival signif icantly in univariate survival analysis (Kaplan-Meier method, p < 0.05) in contrast to VEGF and TSP-1 expression. In Cox regression analysis, however, no independent prognostic impact remained. In conclusion, moderate or stro ng VEGF expression was significantly associated with high microvessel densi ty and TAM count was increased in a subgroup of aggressive tumours. High TA M density was significantly associated with reduced survival in univariate analysis. Int. J. Cancer (Pred. Oncol.) 84:539-543, 1999, (C) 1999 Wiley-Li ss, Inc.