Vascular endothelial growth factor and its soluble receptor in benign and malignant ovarian tumors.
An imbalance between pro-angiogenic and anti-angiogenic factors is hypothesized in the pathogenesis of ovarian cystic disease. The aim of the following study was to explore the possible role of free vascular endothelial growth factor receptor 1 (sVEGFR-1), a soluble regulator of vascular endothelial growth factor (VEGF) action, in ovarian cystoadenoma, endometriomata and cystoadenocarcinoma. Forty-eight women, of whom fourteen had ovarian serous cysts, twenty-eight had stage III-IV ovarian endometriomata, and six had stage IIIB-IIIC ovarian carcinoma, were included. Sampling of serum, peritoneal and ovarian cystic fluids and of tumor tissue was performed before, during and following surgery, respectively. Levels of VEGF and sVEGFR-1 were measured in serum, peritoneal and cystic fluid. VEGF and sVEGFR-1 expression was evaluated in tumor tissue. There were no differences in serum VEGF and sVEGFR-1 levels nor in VEGF/VEGFR-1 ratio between study groups. Peritoneal fluid VEGF levels were higher in cystoadenocarcinoma patients than in endometriosis and in cystoadenoma patients, while sVEGFR-1 peritoneal fluid concentrations were significantly higher only in endometriosis-affected women. VEGF/VEGFR-1 ratio was highest in the peritoneal fluid of cancer patients with respect to the other two groups of women. Cystic fluid VEGF and VEGFR-1 concentrations were higher in endometriomata and in cystoadenocarcinomas than in cystadenomas but the VEGF/VEGFR-1 ratio was highest in cancer patients. Western blot evidenced a marked expression of VEGF and soluble VEGFR-1 in endometriosis tissue with respect to benign cyst tissue but a lower expression of both molecules, contrary to that expected, in cancer tissue. In conclusion, all in all, our data indicate that an excess of local VEGF with respect to its soluble receptor VEGFR-1 may be a key factor in the onset and maintenance of pathological neo-angiogenesis in ovarian cyst formation.
Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Via Roma 67, 56126 Pisa, Italy. g.artini@obgyn.med.unipi.it
Paolo Giovanni
PG
Artini
Maria
M
Ruggiero
Patrizia
P
Monteleone
Angelo
A
Carpi
Francesca
F
Cristello
Vito
V
Cela
Andrea Riccardo
AR
Genazzani
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000737:chemistry; D020420:Cyst Fluid / Q000737:chemistry; D003536:Cystadenocarcinoma / Q000378:metabolism; D003537:Cystadenoma / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D010048:Ovarian Cysts / Q000378:metabolism / Q000503:physiopathology; D010049:Ovarian Diseases / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1