Effect of neoadjuvant chemoradiotherapy on angiogenesis in oesophageal cancer

Background: Vascular endothelial growth factor (VEGF) levels are raised in the serum of patients with oesophageal carcinoma. The aim of this study was to evaluate the tumour microvasculature and the role of tumour-associated macrophages in VEGF production after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer. Methods: Sections from 92 consecutively resected oesophageal tumours were stained for VEGF, von Willebrand factor and CD68. Twenty-seven patients received preoperative chemoradiation and 65 underwent surgical excision alone. The cellular source of VEGF was determined by parallel-section staining. Microvessel density and macrophage count were determined for each tumour by means of image analysis software. Results: There were no significant differences between the two groups in age, sex or tumour type. Local downstaging of disease was evident in most specimens of tumours that had received preoperative chemoradiation. All tumours stained positive for VEGF, including those demonstrating a complete pathological response. Staining of parallel sections confirmed macrophages as the principal source of VEGF. Mean microvessel density was 6.4 per high-power field (h.p.f.) in tumours that received preoperative chernoradiation compared with 5.3 per h.p.f. in those treated by surgery alone (P = 0.130). A significant increase in tumour-associated macrophage infiltration was noted in tumours treated with neoadjuvant chemoradiation (22.1 per h.p.f.) compared with those treated by surgery alone (14.3 per h.p.f.) (P = 0.042). Conclusion: Preoperative chemoradiation had little effect on the local angiogenic profile of the tumour in patients with oesophageal cancer. Tumour-infiltrating macrophages seem to be the source of persistent VEGF production after chemoradiotherapy and might explain the raised serum levels. Addition of an antiangiogenic agent to this regimen may be worthwhile in patients with oesophageal carcinoma.