title: Does soluble fms-like tyrosine kinase-1 regulate placental invasion? Insight from the invasive placenta.
abstract: OBJECTIVE
  Soluble fms-like tyrosine kinase (sFLT-1) is a potent antiangiogenic growth factor that has been found to be markedly elevated in preeclampsia. In healthy pregnancy, serum sFLT-1 concentrations are 50-fold higher than in the nonpregnant state. The functional significance of this physiologic elevation in serum sFLT-1 in normal pregnancy is unknown. We hypothesized that sFLT-1 regulates placental cytotrophoblast invasion and that lower levels of sFLT-1 would be observed locally in invasive placentas (accreta/increta/percreta).
  
  
  METHODS
  We performed a retrospective case-control study comparing placental sFLT-1 expression in hysterectomy specimens from 3 groups: group 1, focally invasive placenta; group 2, normal invasion from the same specimen; and group 3, normal invasion associated with placenta previa. Immunohistochemistry for sFLT-1 was performed, and staining intensity was graded on a scale from 1+ (weak) to 5+ (strong).
  
  
  RESULTS
  We identified 10 hysterectomy specimens from women with invasive placentation and 3 with placenta previa. The median sFLT-1 staining score for group 1 was 1.75 compared to 4.0 for group 2 (P = .01). A significant difference was also found between group 1 and group 3 (P = .01). When comparing depth of invasion, there was a trend toward lower staining score as depth of invasion increased (P = .11). Interobserver agreement for immunohistochemistry scoring was 87%.
  
  
  CONCLUSIONS
  Lower levels of sFLT-1 protein expression were associated with invasive placentation suggesting a critical functional role for sFLT-1 in regulation of placental invasion.
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA.
authors.forename: Kerry
authors.initials: K
authors.lastname: McMahon
authors.affiliation: Howard Hughes Medical Institute and the Departments of Medicine and Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: Stillman
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cummings
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Patton
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Easterling
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism*; D010922:Placenta Diseases / Q000201:enzymology* / Q000601:surgery; D011247:Pregnancy; D012189:Retrospective Studies; D014327:Trophoblasts / Q000201:enzymology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: placenta percreta; soluble fms-like tyrosine kinase; vascular endothelial growth factor