Vascular endothelial growth factor expression in ovarian cancer: a model for targeted use of novel therapies?
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Duncan
Timothy J
TJ
Academic and Clinical Department of Oncology, University of Nottingham, Nottingham, UK.
Al-Attar
Ahmad
A
Rolland
Phil
P
Scott
Ian V
IV
Deen
Suha
S
Liu
David T Y
DT
Spendlove
Ian
I
Durrant
Lindy G
LG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A