Vascular endothelial growth factors and their receptors and regulators in gestational trophoblastic diseases and normal placenta.
OBJECTIVE
To study the expression of vascular endothelial growth factors (VEGFs), placental growth factor (PLGF) and their receptors (VEGFR-1, -2, -3) and their regulators (IL-6, CD147) in normal placenta and gestational trophoblastic disease (GTD) in order to evaluate their potential role in the biology of GTD.


METHODS
Paraffin sections of 10 normal, first-trimester placentas, 10 partial moles, 10 complete moles, 5 choriocarcinomas and 5 placental site trophoblastic tumors (PSTTs) were studied immunohistochemically for expression of VEGFR-1, VEGFR-2, VEGFR-3, IL-6, PLGF and CD147. Immunolocalization of VEGF, Angiopoietin-1 and Angiopoietin-2 was performed on 5 choriocarcinomas and 5 PSTTs. The levels of VEGF and VEGFR-2 were determined in supernatants and lysates of normal trophoblast, JEG-3 and JAR choriocarcinoma cells with electrochemiluminescence assays.


RESULTS
The normal placenta had significantly stronger expression of VEGFR-2 than did those of partial and complete mole (p = 0.001, p = 0.003). VEGF, Angiopoietin-1 and Angiopoietin-2 expression in PSTT were significantly higher than those in choriocarcinoma (p = 0.002, p= 0.01, p = 0.038). Choriocarcinoma showed stronger intensity of staining for VEGFR-3 than did normal placenta, partial and complete mole (p = 0.036, p = 0.038, p = 0.05). Choriocarcinoma had significantly stronger staining of CD147 than did partial and complete mole (p<0.01, p<0.01). PSTT exhibited significantly stronger staining for IL-6 than did choriocarcinoma (p = 0.03).


CONCLUSIONS
PSTTs exhibited strong staining for VEGF, and choriocarcinoma showed strong staining for VEGFR-3. Agents that inhibit the activity of VEGF and VEGF receptors may prove to be useful in the therapy of gestational trophoblastic neoplasia.
Department of Obstetrics and Gynecology, University of Szeged, Szeged, Hungary.
Margit
M
Singh
David
D
Kindelberger
Zoltan
Z
Nagymanyoki
Shu-Wing
SW
Ng
Charles M
CM
Quick
Hidemi
H
Yamamoto
Raina
R
Fichorova
Vilmos
V
Fulop
Ross S
RS
Berkowitz
D042683:Angiopoietin-1 / Q000032:analysis; D042702:Angiopoietin-2 / Q000032:analysis; D051926:Basigin / Q000032:analysis; D002460:Cell Line; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000737:chemistry; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis; D010920:Placenta / Q000737:chemistry*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis*; D014594:Uterine Neoplasms / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C497886:BSG protein, human; D015850:Interleukin-6; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D051926:Basigin; D000072483:Placenta Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3