Vascular endothelial growth factors and their receptors and regulators in gestational trophoblastic diseases and normal placenta

Margit Singh, David Kindelberger, Zoltan Nagymanyoki, Shu Wing Ng, Charles M. Quick, Hidemi Yamamoto, Raina Fichorova, Vilmos Fulop, Ross S. Berkowitz

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16 Citations (Scopus)

Abstract

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. Study Design: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)197-203
Number of pages7
JournalJournal of Reproductive Medicine
Volume57
Issue number5-6
Publication statusPublished - Nov 22 2012

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Keywords

  • CD147
  • Gestational trophoblastic disease
  • IL-6
  • Interleukin-6
  • Placenta growth factor
  • Placental-site trophoblastic tumor
  • VEGFR-1
  • VEGFR-2
  • VEGFR-3
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Singh, M., Kindelberger, D., Nagymanyoki, Z., Ng, S. W., Quick, C. M., Yamamoto, H., Fichorova, R., Fulop, V., & Berkowitz, R. S. (2012). Vascular endothelial growth factors and their receptors and regulators in gestational trophoblastic diseases and normal placenta. Journal of Reproductive Medicine, 57(5-6), 197-203.