Kerry McMahon1, S Ananth Karumanchi2, Isaac E Stillman3, Peter Cummings1, Dorothy Patton1, Thomas Easterling1. 1. Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA. 2. Howard Hughes Medical Institute and the Departments of Medicine and Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA. 3. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA.
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). STUDY DESIGN: 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%. CONCLUSION: 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.
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). STUDY DESIGN: 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%. CONCLUSION: 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.
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