Accreta complicating complete placenta previa is characterized by reduced systemic levels of vascular endothelial growth factor and by epithelial-to-mesenchymal transition of the invasive trophoblast

Am J Obstet Gynecol. 2011 May;204(5):411.e1-411.e11. doi: 10.1016/j.ajog.2010.12.027. Epub 2011 Feb 12.

Abstract

Objective: We sought to characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta, or percreta shares features of epithelial-to-mesenchymal transition.

Study design: We analyzed gestational age-matched serum samples from 90 pregnant women with either complete placenta previa (n = 45) or uncomplicated pregnancies (n = 45). Vascular endothelial growth factor (VEGF), placental growth factor, and soluble form of fms-like-tyrosine-kinase-1 were immunoassayed. VEGF and phosphotyrosine immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7.

Results: Women with previa and invasive placentation (accreta, n = 5; increta, n = 6; percreta, n = 2) had lower systemic VEGF (invasive previa: median 0.8 [0.02-3.4] vs control 6.5 [2.7-10.5] pg/mL, P = .02). VEGF and phosphotyrosine immunostaining predominated in the invasive extravillous trophoblasts that coexpressed vimentin and cytokeratin-7, an epithelial-to-mesenchymal transition feature and tumorlike cell phenotype.

Conclusion: Lower systemic free VEGF and a switch of the interstitial extravillous trophoblasts to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Keratin-7 / metabolism
  • Phosphotyrosine / metabolism
  • Placenta Accreta / metabolism*
  • Placenta Accreta / pathology
  • Placenta Growth Factor
  • Placenta Previa / metabolism*
  • Placenta Previa / pathology
  • Pregnancy
  • Pregnancy Proteins / blood
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / blood
  • Vimentin / metabolism

Substances

  • Keratin-7
  • PGF protein, human
  • Pregnancy Proteins
  • Vascular Endothelial Growth Factor A
  • Vimentin
  • Placenta Growth Factor
  • Phosphotyrosine
  • Vascular Endothelial Growth Factor Receptor-1