The Role of M1 and M2 Macrophages in the Progression of Endometrial Hyperplasia to Endometrioid Adenocarcinoma

Background: The progression of endometrial pathologies, from benign hyperplasia to malignant adenocarcinoma, involves complex interactions between the immune microenvironment, hormonal receptor dynamics, and systemic conditions. This study aims to evaluate immune markers, such as M1/M2 macrophage ratios and tumour-infiltrating lymphocytes (TILs), alongside estrogen (ER) and progesterone (PR) receptor expression in different endometrial conditions. Methods: This retrospective study included 120 cases categorised into three groups: endometrial hyperplasia without atypia, hyperplasia with atypia, and endometrial endometrioid adenocarcinoma. Immune markers (M1/M2 ratio, TILs) and hormonal receptors (ER, PR) were assessed using immunohistochemistry. Statistical comparisons were conducted across diagnostic groups stratified by age and systemic conditions. Results: The M1/M2 Ratio declined progressively from hyperplasia without atypia (mean: 2.0) to adenocarcinoma (mean: 0.5, p < 0.01), indicating a shift from a pro-inflammatory to an immunosuppressive microenvironment. TILs %: Minimal in hyperplasia without atypia (0%), increasing significantly in adenocarcinoma (mean: 15%, p < 0.01). ER/PR expression decreased from hyperplasia without atypia (ER: 80%, PR: 70%) to adenocarcinoma (ER: 30%, PR: 20%, p < 0.01). Premenopausal women exhibited higher receptor expression than postmenopausal women (p < 0.05). Conclusion: This study demonstrates the critical role of immune and hormonal markers in the progression of endometrial diseases. The decline in M1/M2 ratios, rising TILs, and reduced ER/PR expression correlate with disease severity and systemic conditions. These findings suggest the potential of targeting the immune microenvironment and hormonal pathways for personalised therapeutic strategies. Future research should explore the molecular mechanisms underlying these changes and validate these biomarkers in prospective studies.