Immunohistochemical Analysis of IRE1 and PERK Expression in Extravillous Trophoblast Cells of Placenta Accreta Spectrum and Associations With Clinicopathological Parameters

Background/Aim: Placenta accreta spectrum (PAS) is characterized by abnormal placental adherence/invasion at a scarred implantation bed. Endoplasmic reticulum (ER) stress signaling via inositol-requiring enzyme 1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) shapes trophoblast behavior, but its interface-specific role in PAS is unclear. We evaluated IRE1 and PERK immunoreactivity in extravillous trophoblast (EVT) subsets to test associations with PAS severity and maternal outcomes. Patients and Methods: In a retrospective series from a tertiary center, cesarean hysterectomy specimens for PAS and gestational age-matched cesarean controls were analyzed. Immunohistochemistry for IRE1 and PERK was performed on basal plate regions, with semiquantitative immunoreactivity score (IRS:0-12) recorded for EVT subtypes. Associations with clinicopathological parameters and with negative controls were examined with bivariate analyses. Results: IRE1 expression showed no significant associations with clinicopathological parameters. PERK IRS was significantly higher in PAS obstetrical hysterectomy specimens than in controls (mean 9.40±1.96 vs. 4.17±1.52; p