Evaluation and characterization of intraepithelial lymphocytes in normal endometrium, endometrial hyperplasia without atypia, endometrioid intraepithelial neoplasia, and endometrioid endometrial carcinoma

In this study, the intraepithelial distribution of immunohistochemical markers TCR γ/δ, CD3, CD4, CD8, and IFN-γ was evaluated across four diagnostic groups of the endometrium: benign curettage, endometrial hyperplasia without atypia (AEH), endometrial intraepithelial neoplasia (EIN), and endometrioid endometrial carcinoma (ECC). Among a total of 75 patients, 58.6% were in the ECC group. Significant differences were observed among the diagnostic groups in intraepithelial TCR γ/δ (p=0.024), CD3 (p=0.001), and CD8 (p<0.001) expression. The density of TCR γ/δ cells was significantly higher in the EIN group compared to ECC cases, whereas CD3 and CD8 levels were markedly increased in ECC. A decrease in epithelial TCR γ/δ cell counts was observed with increasing depth of myometrial invasion (p=0.046). The intensity and extent of IFN-γ staining were significantly higher in cases with lymphovascular invasion (p=0.008). Composite Immune Activation Index-I was elevated in the ECC group, while Index-II was higher in EIN cases. These findings suggest that, within the endometrium, CD8⁺ cytotoxic T cells and γ/δ T cells may play important roles in the transition from premalignant lesions to malignant transformation.