Endometrioid Immunohistochemical Prognostic Score Integrating SIRT1, HMGB1, Bcl-2, and Caspase-3 Expression in Endometrioid-Type Endometrial Cancer

Background/Objectives: Prognostic stratification of stage I endometrioid-type endometrial cancer remains imperfect when based on clinicopathological variables alone. This retrospective study evaluated immunohistochemical markers reflecting stress adaptation, inflammatory signaling, autophagy regulation, and apoptotic balance, and developed an exploratory Endometrioid Immunohistochemical Prognostic Score (EIPS) based on SIRT1, HMGB1, Bcl-2, and Caspase-3 expression. Methods: Using surgical specimens from 139 patients with stage I endometrioid-type endometrial cancer, EIPS was calculated by assigning one point for high SIRT1, high HMGB1, high Caspase-3, and low Bcl-2 expression. Associations with overall survival and model discrimination were evaluated using Kaplan–Meier analysis, Cox regression, ridge-penalized multivariable modeling, and ROC/AUC analysis. Results: During a median follow-up of 1577 days, 12 deaths occurred. High SIRT1, HMGB1, and Caspase-3 expression were associated with poorer overall survival, while low Bcl-2 was retained as a biologically plausible adverse component. EIPS stratified patients into ordered low-, intermediate-, and high-risk groups with increasing event rates and showed higher apparent mortality discrimination than the predefined LVSI/grade-based clinicopathologic grouping (AUC = 0.857 vs. 0.756). IE-EIPS provided a modest additional apparent improvement in discrimination (AUC = 0.876). Conclusions: EIPS may offer prognostic stratification in stage I endometrioid-type endometrial cancer by integrating biologically complementary immunohistochemical markers.