Assessment of FOXP3+ Expression in Endometrial Precancerous and Neoplastic Lesions: A Comparative Study of Immune Microenvironment Dynamics
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Background: Endometrial carcinoma is a leading cause of cancer-related mortality in women, with distinct subtypes such as endometrioid and serous carcinoma exhibiting varying clinical behaviours. Regulatory T cells (Tregs), marked by FOXP3 expression, play a crucial role in immune modulation within the tumour microenvironment. Programmed cell death ligand 1 (PDL1) is another key immune checkpoint molecule associated with immune evasion in various malignancies. This study investigates the expression of FOXP3 and PDL1 in benign and malignant endometrial lesions, comparing endometrial hyperplasias, endometrioid adenocarcinoma, and serous carcinoma. Methods: 150 cases were analysed, including 80 benign hyperplasias (with and without atypia) and 70 malignant lesions (endometrioid and serous carcinoma). FOXP3 and PDL1 expression levels were assessed using immunohistochemistry, and statistical analyses were performed to evaluate the correlation between these markers and clinicopathological features such as age, tumour stage, and histological subtype. Results: FOXP3 expression was significantly higher in malignant lesions (mean 22-30%) compared to benign hyperplasias (mean 5%). Serous carcinoma exhibited the highest FOXP3 expression (30%), followed by endometrioid carcinoma (22%). PDL1 expression was also significantly higher in malignant tumours, with serous carcinoma showing a mean expression of 12% compared to 6% in endometrioid carcinoma. A positive correlation between FOXP3 and PDL1 expression was observed (Spearman’s correlation coefficient = 0.75, p<0.001). Additionally, higher FOXP3 and PDL1 expressions were observed in advanced-stage tumours (pT2) compared to early-stage tumours (pT1). Conclusion: The study demonstrates that FOXP3-positive Tregs and PDL1 are significantly upregulated in malignant endometrial tumours, particularly in serous carcinoma, associated with a more aggressive clinical course. The positive correlation between FOXP3 and PDL1 expression suggests a potential mechanism of immune evasion and supports immune checkpoint inhibition as a therapeutic strategy in endometrial carcinoma.
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