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Clinical Cancer Research Vol. 8, 3193-3197, October 2002
© 2002 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Preoperative Serum Vascular Endothelial Growth Factor Levels

Significance in Ovarian Cancer1

Brian C. Cooper, Justine M. Ritchie, Carrie L. W. Broghammer, Jeremy Coffin, Joel I. Sorosky, Richard E. Buller, Mary J. C. Hendrix and Anil K. Sood2

Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology [B. C. C., C. L. W. B., J. C., J. I. S., R. E. B., A. K. S.], Biostatistics [J. M. R.], and Anatomy and Cell Biology [M. J. C. H.], Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242

Purpose: To assess the clinical relevance of serum vascular endothelial growth factor (VEGF) levels in distinguishing patients with ovarian cancer from those with benign adnexal masses.

Experimental Design: Preoperative serum VEGF levels were assessed in 101 women with invasive epithelial ovarian cancer, 16 with low malignant potential (LMP) ovarian tumors, and 34 women with benign ovarian tumors. VEGF levels were determined using an ELISA (R&D Systems, Minneapolis, MN).

Results: Ovarian cancer patients had a mean preoperative VEGF level of 549 pg/ml (median 379 pg/ml), which was significantly higher than those with benign adnexal masses (mean 228 pg/ml, median 155 pg/ml; P < 0.001) and LMP tumors (mean 200 pg/ml, median 129 pg/ml; P < 0.001). There were no significant differences in VEGF levels between individuals with benign masses and LMP tumors. The ability of VEGF to differentiate malignancy from benign masses at a cutoff VEGF level of 246 pg/ml gave a sensitivity of 74%, a specificity of 71%, a positive predictive value of 88%, and a negative predictive value of 48%. VEGF levels were also significantly higher in patients with stage I ovarian cancer compared with those with benign disease or LMP tumors. Among patients with ovarian cancer, there were no significant differences in VEGF levels based on age, stage, grade, or level of cytoreduction. The presence of ascites was associated with a significantly higher VEGF level (mean 667 pg/ml, median 445 pg/ml versus mean 317 pg/ml, median 293 pg/ml; P < 0.001). Various preoperative VEGF levels were assessed as a predictor of survival, and a VEGF level >380 pg/ml was associated with a hazard ratio of 2.13 (P = 0.009) by univariate analysis. In multivariate analysis of age, stage, cytoreduction, preoperative CA-125, grade, ascites, and VEGF levels above 380 pg/ml, only VEGF levels >380 pg/ml (hazard ratio 2.33; P = 0.02) and advanced stage (hazard ratio 9.03; P = 0.004) were significant.

Conclusions: Preoperative VEGF levels may be useful in differentiating benign adnexal masses from malignancy. Preoperative VEGF levels >380 pg/ml are an independent risk factor for death because of disease.




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