Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma.
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.
Yokoyama
Y
Y
Department of Obstetrics and Gynaecology, University of Cambridge, The Rose Maternity Hospital, UK. yokoyama@cc.hirosaki-u.ac.jp
Charnock-Jones
D S
DS
Licence
D
D
Yanaihara
A
A
Hastings
J M
JM
Holland
C M
CM
Emoto
M
M
Umemoto
M
M
Sakamoto
T
T
Sato
S
S
Mizunuma
H
H
Smith
S K
SK
D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000473:pathology; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D012189:Retrospective Studies; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3