title: 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.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Lower systemic free VEGF and a switch of the interstitial extravillous trophoblasts to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. mark.j.wehrum@us.army.mil
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Wehrum
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
authors.forename: Carolyn
authors.initials: C
authors.lastname: Salafia
authors.forename: Stephen
authors.initials: S
authors.lastname: Thung
authors.forename: Mert O
authors.initials: MO
authors.lastname: Bahtiyar
authors.forename: Erica F
authors.initials: EF
authors.lastname: Werner
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Campbell
authors.forename: Christine
authors.initials: C
authors.lastname: Laky
authors.forename: Anna K
authors.initials: AK
authors.lastname: Sfakianaki
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Funai
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053552:Keratin-7 / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D010921:Placenta Accreta / Q000378:metabolism* / Q000473:pathology; D000072483:Placenta Growth Factor; D010923:Placenta Previa / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014746:Vimentin / Q000378:metabolism
chemical_list: D053552:Keratin-7; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D000072483:Placenta Growth Factor; D019000:Phosphotyrosine; D040281:Vascular Endothelial Growth Factor Receptor-1