Expression of pluripotency stem cell markers in endometrial hyperplasia

Background: Endometrial hyperplasia, a precursor to endometrial cancer, is increasing due to rising obesity and lifestyle risks. Scarce data exist on the molecular characterization of endometrial hyperplasia for prognostic and preventive applications, Objectives: This study investigates the expression of core pluripotency stem cell markers in endometrial hyperplasia, given their emerging role in cancer stem cell regulation in various cancers, including endometrial cancer, Design: This is a case–control study utilizing archival endometrial tissue blocks. In this study, we assessed the immunohistochemical expression of NANOG, OCT4, and SOX2 in hyperplastic endometrium compared to benign non-hyperplastic endometrium obtained from women with abnormal uterine bleeding, Results: The investigation included 165 patients (83 cases with endometrial hyperplasia and 82 controls). The prevalence of endometrial hyperplasia in our cohort was 20.8% (of 500 patients). NANOG showed moderate to high expression in 60.2% of endometrial hyperplasia cases, significantly higher than in controls (19.5%), p < 0.0005. OCT4 showed moderate/high expression in 12% of endometrial hyperplasia cases compared to 3.7% of controls ( p = 0.045). In comparison, SOX2 was expressed in 18% of endometrial hyperplasia with no significant difference from controls (19.7%), p = 0.823. Logistic regression showed that age and NANOG expression were significant predictors of endometrial hyperplasia risk, with women exhibiting moderate/high NANOG expression having an 11-fold increased risk of endometrial hyperplasia (95% confidence interval of odds ratio: 3.484–35.864, p < 0.001). Using receiver operating characteristic curves, women’s age predicted SOX2 expression in endometrial hyperplasia cases (area under the curve (AUC) = 0.867, cutoff = 49 years, Youden’s index = 0.722, sensitivity = 100%, specificity = 72.2%, p < 0.001), and NANOG in controls (AUC = 0.734, cutoff = 42 years, Youden’s index = 0.37, sensitivity = 68.8%, specificity = 68.2%, p = 0.004). Conclusion: NANOG shows promise for a potential predictive role in patients with endometrial hyperplasia, with moderate/high expression indicating a higher risk. SOX2’s role was unclear but age-related. Further studies are needed to validate these findings and explore hormonal links.