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Vascular Endothelial Growth Factor Expression in Ovarian Cancer: A Model for Targeted Use of Novel Therapies?

Authors' Affiliations: ¹ Academic and Clinical Department of Oncology, University of Nottingham; ² Division of Histopathology and ³ Department of Obstetrics and Gynaecology, University Hospitals Nottingham, Nottingham, United Kingdom and ⁴ Department of Obstetrics and Gynaecology, Derby City General Hospital, Derby, United Kingdom

Requests for reprints: Lindy G. Durrant, Institute of Infections and Immunity, University of Nottingham, Nottingham City Hospital NHS Trust, Hucknall Road, Nottingham NG5 1PB, United Kingdom. Phone: 44-115-82-31862; Fax: 44-115-82-31849/44-121-353-1482; E-mail: lindy.durrant{at}nottingham.ac.uk.

Purpose: Angiogenesis has a vital role in tumor growth and metastasis, and vascular endothelial growth factor (VEGF) represents a potent cytokine in this process. However, the influence of VEGF in ovarian cancer remains controversial. Interest has focused on the use of antiangiogenic drugs in ovarian cancer. This study aims to establish the pattern of expression and effect on prognosis of VEGF in a large population of ovarian cancer patients and to potentially identify a cohort in whom antiangiogenic therapy is appropriate.

Experimental Design: Using a tissue microarray of 339 primary ovarian cancers, the expression of VEGF was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied.

Results: Tumors expressing high levels of VEGF had significantly poorer survival (P = 0.04). Factors shown to predict prognosis independently of each other were age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. VEGF was independently predictive of prognosis on multivariate analysis (P = 0.02). There was no correlation between VEGF and any clinicopathologic variable. High expression of VEGF was seen in only 7% of the tumors, suggesting that the role of antiangiogenic drugs may be limited to a small subset of patients.

Conclusion: High VEGF expression occurs in a small proportion of ovarian cancers, and this independently predicts poor prognosis. The small percentage of tumors with high levels of VEGF activity suggests that the role of bevacizumab may potentially be limited to a few patients; these patients could be targeted by molecular profiling.