Immunohistochemical Expression of IRE1 and PERK in Breast Cancer: Associations With Clinicopathological Characteristics and Survival Outcomes
Flindris S., Markozannes G., Margioula‐siarkou C., Tsiaras N., Margioula‐siarkou G., Chalitsios C., Sakellariou E., Flindris K., Styliara E., Paschopoulos M., Petousis S., Navrozoglou I., Dinas K.
Background/Aim: This study evaluated the immunohistochemical expression of IRE1 and PERK in breast cancer and explored their associations with clinicopathologic characteristics and survival outcomes. Patients and Methods: A cohort of 72 breast cancer specimens and 16 controls was analyzed for IRE1 and PERK expression using immunohistochemistry. Associations with clinicopathological variables, hormone receptor status, tumor markers and survival outcomes were assessed using statistical analyses, including Kaplan-Meier survival curves and Cox proportional hazard models. Results: IRE1 and PERK expression levels were significantly elevated in breast cancer tissues compared to controls (p<0.001). Strong positive correlation was observed between IRE1 and PERK expression (Spearman’s ρ=0.55, p<0.001). High PERK expression was associated with older age (p=0.038) and tumor grade 3 (p=0.042), while high IRE1 expression correlated with advanced TNM stage (p<0.001), estrogen receptor (p=0.031), progesterone receptor (p=0.028), and human epidermal growth factor receptor 2 positivity (p=0.028), as well as increased Ki-67 index (p=0.003), suggesting a more aggressive tumor phenotype. IRE1 expression was significantly associated with sentinel lymph node positivity (p=0.001) but inversely related to axillary lymph node involvement (p=0.031). Multivariate Cox regression analysis revealed that high IRE1 expression [immunoreactivity score (IRS) 5-12] was linked to an increased mortality risk [hazard ratio (HR)=12.19, 95% confidence interval (CI)=0.99-150.35, p=0.05], and high PERK expression (IRS 4-12) was similarly associated with worse survival (HR=12.10, 95%CI=1.16-126.30, p=0.04). Tumor stage was the strongest predictor of mortality (HR=79.89, p<0.01). Conclusion: High IRE1 and PERK expression levels are associated with aggressive tumor characteristics and reduced survival in breast cancer, underscoring the importance of the unfolded protein response in carcinogenesis and disease progression.