Immunohistochemical Expression of Endoplasmic Reticulum Stress Markers and their Association With Clinicopathological...

This study aimed to examine the immunohistochemical expression of Inositol-Requiring Enzyme 1 Alpha (IRE1) and Protein Kinase R-like ER Kinase (PERK) immunoreactivity scores (IRS) as emerging biomarkers on key clinicopathologic features and survival outcomes in endometrial cancer (EC).

Immunoreactive scores (IRS) for IRE1 and PERK were assessed in tumor samples from 73 EC survivors and compared with 20 benign endometrial controls. Associations between IRS values and clinicopathological variables were analyzed. Overall survival (OS) and disease-free survival (DFS) were evaluated using univariable and multivariable Cox proportional hazards models adjusted for age, FIGO stage, and tumor grade.

IRE1-IRS and PERK-IRS were significantly higher in EC survivors compared to controls (p=0.015 and p<0.001, respectively) and PERK-IRS was higher in non-endometrioid than endometrioid tumors (p=0.017). EC survivors undergoing laparotomy exhibited higher PERK-IRS than those treated laparoscopically (p=0.009). Neither IRE1-IRS nor PERK-IRS was associated with OS or DFS, except for a negative association of high vs. low IRE1-IRS score and DFS in the unadjusted model (p=0.026) but not in the adjusted one.

IRE1 and PERK expression is up-regulated in endometrial cancer and correlates with selected clinicopathological features, particularly those linked to aggressive disease. However, neither marker demonstrated independent prognostic value for survival outcomes. Further studies are warranted to clarify the role of ER stress pathways in EC biology and their potential implications for risk stratification and targeted therapy.