Effect of neoadjuvant chemoradiotherapy on angiogenesis in oesophageal cancer

• Published in: British journal of surgery 2003-11, Vol.90 (11), p.1373-1378
• Main Authors: McDonnell, C. O., Bouchier-Hayes, D. J., Toomey, D., Foley, D., Kay, E. W., Leen, E., Walsh, T. N.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - blood supply; Adenocarcinoma - diagnostic imaging; Adenocarcinoma - drug therapy; Aged; Biological and medical sciences; Carcinoma, Squamous Cell - blood supply; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - radiotherapy; Carcinoma, Squamous Cell - surgery; Chemotherapy, Adjuvant - methods; Combined Modality Therapy - methods; Esophageal Neoplasms - blood supply; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - surgery; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry - methods; Leukocyte Count; Macrophages; Male; Medical sciences; Microcirculation; Neoplasm Staging - methods; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - radiotherapy; Preoperative Care - methods; Radiography; Radiotherapy, Adjuvant - methods; Tumors; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - blood
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1002/bjs.4338

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 chemoradiation 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. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. A rational basis for the use of antiangiogenic compounds in oesophageal cancer