1. ¹Reproductive Molecular Research Group, Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Maternity Hospital, Robinson Way, Cambridge CB2 2SW, UK
2. ²Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, 5-Zaifu-cho, Hirosaki 036-8562, Japan

Correspondence: Dr Y Yokoyama, Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, 5-Zaifu-cho, Hirosaki 036-8562, Japan. E-mail: yokoyama@cc.hirosaki-u.ac.jp

Received 1 July 2002; Revised 3 October 2002; Accepted 10 October 2002.

Abstract

We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis.