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

Abstract

Angiogenesis is a key process in tumour growth and metastasis, and microvessel density has been found to influence the prognosis of endometrial carcinoma patients. Less is known about regulators of angiogenesis. Studies of other tumour types have indicated that the density of tumour-associated macrophages (TAMs) and the expression of vascular endothelial growth factor (VEGF) might stimulate vessel formation, whereas thrombospondin-1 (TSP-1) may inhibit this process. We investigated the influence of TAM (CD68+), VEGF and TSP-1 expression on tumour vascular density and prognosis among endometrial carcinoma patients and compared our findings with clinico-pathological variables and tumour markers. In a prospective study, 60 endometrial carcinoma patients with long (median 11 years) and complete follow-up were included. Intratumour density of TAMs was significantly associated with FIGO stage, histological type, histological grade, DNA index, estradiol receptor concentration, intratumour Ki-67 and p53 protein expression (all p < 0.05). Moderate or strong expression of VEGF was significantly associated with serous papillary/clear cell tumour types, high microvessel density and aneuploidy (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 significantly 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 strong VEGF expression was significantly associated with high microvessel density and TAM count was increased in a subgroup of aggressive tumours. High TAM density was significantly associated with reduced survival in univariate analysis.