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

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Yokoyama, Y 
Charnock-Jones, DS 
Licence, D 
Yanaihara, A 
Hastings, JM 


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.



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

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Br J Cancer

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Springer Science and Business Media LLC