Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer.

Abstract As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml(-1), VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass. Full text PDFSelected References These references are in PubMed. This may not be the complete list of references from this article. - Bancher-Todesca D., Obermair A., Bilgi S., Kohlberger P., Kainz C., Breitenecker G., Leodolter S., Gitsch G. Angiogenesis in vulvar intraepithelial neoplasia. Gynecol Oncol. 1997 Mar;64(3):496–500. doi: 10.1006/gyno.1996.4582. [DOI] [PubMed] [Google Scholar] - Boocock C. A., Charnock-Jones D. S., Sharkey A. M., McLaren J., Barker P. J., Wright K. A., Twentyman P. R., Smith S. K. Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst. 1995 Apr 5;87(7):506–516. doi: 10.1093/jnci/87.7.506. [DOI] [PubMed] [Google Scholar] - Ferrara N., Henzel W. J. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):851–858. doi: 10.1016/0006-291x(89)92678-8. [DOI] [PubMed] [Google Scholar] - Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar] - Gadducci A., Baicchi U., Marrai R., Ferdeghini M., Bianchi R., Facchini V. Preoperative evaluation of D-dimer and CA 125 levels in differentiating benign from malignant ovarian masses. Gynecol Oncol. 1996 Feb;60(2):197–202. doi: 10.1006/gyno.1996.0025. [DOI] [PubMed] [Google Scholar] - Gordon J. D., Mesiano S., Zaloudek C. J., Jaffe R. B. Vascular endothelial growth factor localization in human ovary and fallopian tubes: possible role in reproductive function and ovarian cyst formation. J Clin Endocrinol Metab. 1996 Jan;81(1):353–359. doi: 10.1210/jcem.81.1.8550777. [DOI] [PubMed] [Google Scholar] - Guidi A. J., Abu-Jawdeh G., Berse B., Jackman R. W., Tognazzi K., Dvorak H. F., Brown L. F. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst. 1995 Aug 16;87(16):1237–1245. doi: 10.1093/jnci/87.16.1237. [DOI] [PubMed] [Google Scholar] - Jacobs I. J., Skates S., Davies A. P., Woolas R. P., Jeyerajah A., Weidemann P., Sibley K., Oram D. H. Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study. BMJ. 1996 Nov 30;313(7069):1355–1358. doi: 10.1136/bmj.313.7069.1355. [DOI] [PMC free article] [PubMed] [Google Scholar] - Jacobs I., Bast R. C., Jr The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod. 1989 Jan;4(1):1–12. doi: 10.1093/oxfordjournals.humrep.a136832. [DOI] [PubMed] [Google Scholar] - Kamat B. R., Brown L. F., Manseau E. J., Senger D. R., Dvorak H. F. Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells. Role in corpus luteum development. Am J Pathol. 1995 Jan;146(1):157–165. [PMC free article] [PubMed] [Google Scholar] - Ke-Lin, Qu-Hong, Nagy J. A., Eckelhoefer I. A., Masse E. M., Dvorak A. M., Dvorak H. F. Vascular targeting of solid and ascites tumours with antibodies to vascular endothelial growth factor. Eur J Cancer. 1996 Dec;32A(14):2467–2473. doi: 10.1016/s0959-8049(96)00391-7. [DOI] [PubMed] [Google Scholar] - Klauber N., Rohan R. M., Flynn E., D'Amato R. J. Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Nat Med. 1997 Apr;3(4):443–446. doi: 10.1038/nm0497-443. [DOI] [PubMed] [Google Scholar] - Kondo S., Asano M., Matsuo K., Ohmori I., Suzuki H. Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients. Biochim Biophys Acta. 1994 Mar 31;1221(2):211–214. doi: 10.1016/0167-4889(94)90016-7. [DOI] [PubMed] [Google Scholar] - Markowska J., Kopczyński Z., Szewierski Z., Markowski M., Niecewicz R. The value of estimating CA 125 in fluids from benign or malignant cysts, in the exudate and blood serum in women with ovarian cancer. Eur J Gynaecol Oncol. 1994;15(1):29–32. [PubMed] [Google Scholar] - Mattern J., Stammler G., Koomagi R., Wallwiener D., Kaufmann M., Volm M. Association of vascular endothelial growth factor expression with tumor cell proliferation in ovarian carcinoma. Anticancer Res. 1997 Jan-Feb;17(1B):621–624. [PubMed] [Google Scholar] - Melnyk O., Shuman M. A., Kim K. J. Vascular endothelial growth factor promotes tumor dissemination by a mechanism distinct from its effect on primary tumor growth. Cancer Res. 1996 Feb 15;56(4):921–924. [PubMed] [Google Scholar] - Neufeld G., Cohen T., Gitay-Goren H., Poltorak Z., Tessler S., Sharon R., Gengrinovitch S., Levi B. Z. Similarities and differences between the vascular endothelial growth factor (VEGF) splice variants. Cancer Metastasis Rev. 1996 Jun;15(2):153–158. doi: 10.1007/BF00437467. [DOI] [PubMed] [Google Scholar] - Obermair A., Bancher-Todesca D., Bilgi S., Kaider A., Kohlberger P., Müllauer-Ertl S., Leodolter S., Gitsch G. Correlation of vascular endothelial growth factor expression and microvessel density in cervical intraepithelial neoplasia. J Natl Cancer Inst. 1997 Aug 20;89(16):1212–1217. doi: 10.1093/jnci/89.16.1212. [DOI] [PubMed] [Google Scholar] - Oram D. H., Jeyarajah A. R. The role of ultrasound and tumour markers in the early detection of ovarian cancer. Br J Obstet Gynaecol. 1994 Nov;101(11):939–945. doi: 10.1111/j.1471-0528.1994.tb13035.x. [DOI] [PubMed] [Google Scholar] - Senger D. R., Galli S. J., Dvorak A. M., Perruzzi C. A., Harvey V. S., Dvorak H. F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983–985. doi: 10.1126/science.6823562. [DOI] [PubMed] [Google Scholar] - Soker S., Svahn C. M., Neufeld G. Vascular endothelial growth factor is inactivated by binding to alpha 2-macroglobulin and the binding is inhibited by heparin. J Biol Chem. 1993 Apr 15;268(11):7685–7691. [PubMed] [Google Scholar] - Takano S., Yoshii Y., Kondo S., Suzuki H., Maruno T., Shirai S., Nose T. Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res. 1996 May 1;56(9):2185–2190. [PubMed] [Google Scholar] - Terman B. I., Dougher-Vermazen M. Biological properties of VEGF/VPF receptors. Cancer Metastasis Rev. 1996 Jun;15(2):159–163. doi: 10.1007/BF00437468. [DOI] [PubMed] [Google Scholar] - Woolas R. P., Conaway M. R., Xu F., Jacobs I. J., Yu Y., Daly L., Davies A. P., O'Briant K., Berchuck A., Soper J. T. Combinations of multiple serum markers are superior to individual assays for discriminating malignant from benign pelvic masses. Gynecol Oncol. 1995 Oct;59(1):111–116. doi: 10.1006/gyno.1995.1276. [DOI] [PubMed] [Google Scholar] - Yeo K. T., Sioussat T. M., Faix J. D., Senger D. R., Yeo T. K. Development of time-resolved immunofluorometric assay of vascular permeability factor. Clin Chem. 1992 Jan;38(1):71–75. [PubMed] [Google Scholar] - Yeo K. T., Wang H. H., Nagy J. A., Sioussat T. M., Ledbetter S. R., Hoogewerf A. J., Zhou Y., Masse E. M., Senger D. R., Dvorak H. F. Vascular permeability factor (vascular endothelial growth factor) in guinea pig and human tumor and inflammatory effusions. Cancer Res. 1993 Jun 15;53(12):2912–2918. [PubMed] [Google Scholar]