In vivo (Athens, Greece) · 2026
Immunohistochemical Analysis of IRE1 and PERK Expression in Extravillous Trophoblast Cells of Placenta Accreta Spectrum and Associations With Clinicopathological Parameters.
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Flindris Stefanos, Christopoulos Konstantinos, Gouta Chrysoula, Yfanti Christina, Tsiaras Nikolaos, Savvidou Nikoleta-Dimitra, Kalinderis Michail, Traianos Alexandros, Sidiropoulos Apostolos, Tsakmaki Evangelia, Tsitsila Konstantina, Empilouk Elif, Romanidou Liountmila, Sakellariou Eleni, Flindris Konstantinos, Styliara Effrosyni, Pantazis Konstantinos, Dinas Konstantinos, Margioula-Siarkou Chrysoula, Petousis Stamatios, Angelidou Stamatia
Аннотация
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<0.001). Across PAS subtypes (accreta/increta/percreta), PERK-IRS varied numerically but not significantly. Within PAS, PERK-IRS was negatively associated with maternal complications (p=0.035).
CONCLUSION: PERK-IRS was elevated at the stressed implantation interface in PAS relative to normal placentation, while IRE1 showed no clear differential signal with the current assay. Paradoxically, within PAS, lower local PERK-IRS signal correlated with complications, suggesting that the magnitude/timing of PERK engagement may influence operative risk. Larger studies incorporating activation-specific markers are warranted to refine biological stratification and prognostication in PAS.
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<0.001). Across PAS subtypes (accreta/increta/percreta), PERK-IRS varied numerically but not significantly. Within PAS, PERK-IRS was negatively associated with maternal complications (p=0.035).
CONCLUSION: PERK-IRS was elevated at the stressed implantation interface in PAS relative to normal placentation, while IRE1 showed no clear differential signal with the current assay. Paradoxically, within PAS, lower local PERK-IRS signal correlated with complications, suggesting that the magnitude/timing of PERK engagement may influence operative risk. Larger studies incorporating activation-specific markers are warranted to refine biological stratification and prognostication in PAS.