Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2026.009

Comparative study of the endometrial microenvironment's immunohistochemical profile in pre-tumour and tumour conditions: endometrial hyperplasia, endometrioid carcinoma, and serous carcinoma

Paata Jorjoliani, Zaza Bokhua, George Burkadze, Shota Kepuladze
Department of Molecular Pathology, Tbilisi State Medical University, Tbilisi, Georgia

Background: Endometrial carcinogenesis involves complex interactions between hormonal signaling and the local immune microenvironment. While atypical endometrial hyperplasia is a recognized precursor to carcinoma, the spatial and phenotypic evolution of immune and hormonal markers during progression remains incompletely characterized.

Methods: A retrospective cohort of 150 endometrial specimens, including hyperplasia without atypia (n=40), hyperplasia with atypia (n=40), endometrioid carcinoma (n=40), and serous carcinoma (n=30), was analyzed using immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, estrogen receptor (ER), and progesterone receptor (PR). Digital whole-slide imaging and QuPath were applied to quantify immune cell densities in intratumoral and peritumoral compartments. Correlations between immune markers and hormonal receptors were evaluated, and a subgroup of 27 paired hyperplasia-carcinoma cases was analyzed separately.

Results: CD3+ and CD8+ T-cell densities increased progressively from hyperplasia to carcinoma (P<0.001), with hyperplastic lesions demonstrating predominant peritumoral localization consistent with immune exclusion. FOXP3+ regulatory T cells were enriched in neoplastic lesions, particularly in ER/PR-positive tumors. CD8+ intratumoral and peritumoral densities showed significant inverse correlations with ER and PR expression (both r=-0.76, P<0.001), whereas FOXP3+ infiltration correlated positively with ER and PR (r=0.64, P<0.001). M2 CD163+ macrophages demonstrated an inverse association with ER (r=-0.49, P<0.01), while M1 CD68+/iNOS macrophages showed no statistically significant correlations. In the paired subgroup, higher peritumoral than intratumoral CD8+ densities persisted, indicating residual immune exclusion despite malignant transformation.

Conclusions: Endometrial neoplastic progression is characterized by a transition from peritumoral immune exclusion in hyperplasia to increased intratumoral immune infiltration in carcinoma, although this shift is not universal. Hormone receptor-positive tumors exhibit enrichment of FOXP3+ regulatory T cells and CD163+ macrophages, suggesting hormone-linked immune suppression. These findings highlight combined immune-hormonal biomarkers as potential indicators of progression risk and support further investigation of integrated immunomodulatory and hormone-targeted therapeutic strategies.

Keywords: endometrial hyperplasia, endometrioid carcinoma, serous carcinoma, tumor microenvironment, FOXP3, CD8, CD163

Received: October 12, 2025; Revised: March 12, 2026; Accepted: March 20, 2026; Prepublished online: May 8, 2026 

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