Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma

Br J Cancer. 2003 Jan 27;88(2):237-44. doi: 10.1038/sj.bjc.6600701.


We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / diagnosis
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / diagnosis
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cystadenocarcinoma, Serous / diagnosis
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Endothelial Growth Factors / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / diagnosis
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Peritoneal Neoplasms / diagnosis
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / secondary
  • Prognosis
  • Retrospective Studies
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism


  • Biomarkers, Tumor
  • Endothelial Growth Factors
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Vascular Endothelial Growth Factor Receptor-3