Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer

Angiogenesis is esential for tumour growth and metastasis, Vascular endothe lial growth factor (VEGF) is a potent endothelial cell mitogen and is an im portant component of the angiogenic stimulus in a range of human neoplasias , In addition to its mitogenic activities, VEGF has also been found to stim ulate migration in macrophages via the flt-1 VEGF receptor. It has previous ly been shown that increased focal tumour macrophage infiltration is associ ated with increased angiogenesis and,worsened relapse-free and overall surv ival in breast cancer. Macrophages are able to stimulate angiogenesis by th eir production of a range of factors including VEGF, tumour necrosis factor -alpha (TNF-alpha), and thymidine phosphorylase (TP). Thus, in breast cance r, VEGF could have a dual role in the regulation of angiogenesis, by direct mitogenic stimulation of endothelial cells, and also indirectly by attract ing macrophages into avascular tumours, The purpose of this study mas to lo calize VEGF protein in a series of 96 consecutive primary breast carcinomas and to determine its relationship to focal macrophage infiltration (macrop hage index), These two variables mere also compared with the pathological f eatures of the tumours, as well as oestrogen receptor (ER), epidermal growt h factor receptor (EGFR), microvessel density, macrophage index, and surviv al. An inverse relationship (p = 0.0006) was noted between VEGF and EGFR, w ith high VEGF expression correlating with low EGFR levels. In the EGFR-nega tive group of cases (n = 56), positive associations were observed between V EGF expression and macrophage index (p = 0.005), ER (p = 0.05), p53 (p = 0. 006), tumour grade (p = 0.02), and tumour necrosis (p = 0.03), Macrophage c ounts were higher in EGFR-positive tumours (p = 0.0006) and no associations were found between VEGF expression and increased microvessel density. Thes e results show that in breast cancers there are two types of macrophage inf iltrates, one associated with the presence of EGFR and low VEGF expression in tumours and the other with high VEGF expression in EGFR-negative tumours , VEGF expression may be an important factor in the recruitment of tumour-a ssociated macrophages into breast carcinomas and may thus have an additiona l, indirect, pathway of angiogenic stimulation in this type of tumour. Copy right (C) 2000 John Wiley &: Sons, Ltd.