Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(9):1221–1227. doi: 10.1038/bjc.1997.537

Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: correlation with clinicopathology and patient survival, and analysis of serum VEGF levels.

S Yamamoto 1, I Konishi 1, M Mandai 1, H Kuroda 1, T Komatsu 1, K Nanbu 1, H Sakahara 1, T Mori 1
PMCID: PMC2228134  PMID: 9365173

Abstract

Vascular endothelial growth factor (VEGF) is known to be produced by various solid tumours and is thought to be involved in microvascular permeability and/or angiogenesis. To examine the relationship between VEGF expression in ovarian neoplasms and clinicopathological factors or patient survival, expression of VEGF was analysed immunohistochemically in 110 epithelial ovarian tumours. In addition, VEGF levels in the tumour fluid (17 patients), ascites (12 patients) and sera (38 patients) were determined using enzyme immunoassay. Positive immunostaining for VEGF was observed in 97% (68 out of 70) of ovarian carcinomas, which was significantly higher than that of tumours of low malignant potential (LMP) (13 out of 25; 52%) and benign cystadenomas (5 out of 15; 33%) (P < 0.01). In ovarian carcinomas, strong VEGF immunostaining was also observed more frequently in tumours of clear cell type (P < 0.05) in the advanced stage of disease (P < 0.05) and with positive peritoneal cytology (P < 0.01). Patients with strong VEGF staining had poorer survival rates than those with weak or no immunostaining for VEGF (P < 0.01). These findings suggest that strong VEGF expression plays an important role in the tumour progression of ovarian carcinoma. The enzyme immunoassay revealed higher serum VEGF levels in carcinoma patients than those in patients with LMP or benign tumours (P < 0.01). Serum VEGF levels decreased after the successful removal of tumours in ovarian cancer patients and, in one patient, the serum VEGF level was re-elevated during relapse. Therefore, serum VEGF could be used as a marker for monitoring the clinical course of ovarian cancer patients.

Full text

PDF
1221

Images in this article

1224Figure 1
on p.1224

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abu-Jawdeh G. M., Faix J. D., Niloff J., Tognazzi K., Manseau E., Dvorak H. F., Brown L. F. Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms. Lab Invest. 1996 Jun;74(6):1105–1115. [PubMed] [Google Scholar]
  2. Berkman R. A., Merrill M. J., Reinhold W. C., Monacci W. T., Saxena A., Clark W. C., Robertson J. T., Ali I. U., Oldfield E. H. Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J Clin Invest. 1993 Jan;91(1):153–159. doi: 10.1172/JCI116165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brown L. F., Berse B., Jackman R. W., Tognazzi K., Guidi A. J., Dvorak H. F., Senger D. R., Connolly J. L., Schnitt S. J. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol. 1995 Jan;26(1):86–91. doi: 10.1016/0046-8177(95)90119-1. [DOI] [PubMed] [Google Scholar]
  5. Brown L. F., Berse B., Jackman R. W., Tognazzi K., Manseau E. J., Dvorak H. F., Senger D. R. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol. 1993 Nov;143(5):1255–1262. [PMC free article] [PubMed] [Google Scholar]
  6. Brown L. F., Berse B., Jackman R. W., Tognazzi K., Manseau E. J., Senger D. R., Dvorak H. F. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res. 1993 Oct 1;53(19):4727–4735. [PubMed] [Google Scholar]
  7. Connolly D. T., Olander J. V., Heuvelman D., Nelson R., Monsell R., Siegel N., Haymore B. L., Leimgruber R., Feder J. Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017–20024. [PubMed] [Google Scholar]
  8. 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]
  9. Harrison-Woolrych M. L., Sharkey A. M., Charnock-Jones D. S., Smith S. K. Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. J Clin Endocrinol Metab. 1995 Jun;80(6):1853–1858. doi: 10.1210/jcem.80.6.7775632. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Krasnow J. S., Berga S. L., Guzick D. S., Zeleznik A. J., Yeo K. T. Vascular permeability factor and vascular endothelial growth factor in ovarian hyperstimulation syndrome: a preliminary report. Fertil Steril. 1996 Mar;65(3):552–555. [PubMed] [Google Scholar]
  12. Mattern J., Koomägi R., Volm M. Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma. Br J Cancer. 1996 Apr;73(7):931–934. doi: 10.1038/bjc.1996.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nagy J. A., Masse E. M., Herzberg K. T., Meyers M. S., Yeo K. T., Yeo T. K., Sioussat T. M., Dvorak H. F. Pathogenesis of ascites tumor growth: vascular permeability factor, vascular hyperpermeability, and ascites fluid accumulation. Cancer Res. 1995 Jan 15;55(2):360–368. [PubMed] [Google Scholar]
  14. Neufeld G., Tessler S., Gitay-Goren H., Cohen T., Levi B. Z. Vascular endothelial growth factor and its receptors. Prog Growth Factor Res. 1994;5(1):89–97. doi: 10.1016/0955-2235(94)90019-1. [DOI] [PubMed] [Google Scholar]
  15. Neulen J., Yan Z., Raczek S., Weindel K., Keck C., Weich H. A., Marmé D., Breckwoldt M. Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 1995 Jun;80(6):1967–1971. doi: 10.1210/jcem.80.6.7775647. [DOI] [PubMed] [Google Scholar]
  16. Olson T. A., Mohanraj D., Carson L. F., Ramakrishnan S. Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res. 1994 Jan 1;54(1):276–280. [PubMed] [Google Scholar]
  17. Plate K. H., Breier G., Weich H. A., Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature. 1992 Oct 29;359(6398):845–848. doi: 10.1038/359845a0. [DOI] [PubMed] [Google Scholar]
  18. Samoto K., Ikezaki K., Ono M., Shono T., Kohno K., Kuwano M., Fukui M. Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res. 1995 Mar 1;55(5):1189–1193. [PubMed] [Google Scholar]
  19. Senger D. R., Perruzzi C. A., Feder J., Dvorak H. F. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 1986 Nov;46(11):5629–5632. [PubMed] [Google Scholar]
  20. Senger D. R., Van de Water L., Brown L. F., Nagy J. A., Yeo K. T., Yeo T. K., Berse B., Jackman R. W., Dvorak A. M., Dvorak H. F. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev. 1993 Sep;12(3-4):303–324. doi: 10.1007/BF00665960. [DOI] [PubMed] [Google Scholar]
  21. Takahashi A., Sasaki H., Kim S. J., Tobisu K., Kakizoe T., Tsukamoto T., Kumamoto Y., Sugimura T., Terada M. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res. 1994 Aug 1;54(15):4233–4237. [PubMed] [Google Scholar]
  22. 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]
  23. 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]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES