Clinicopathologic and Immunohistochemical Correlates of Disease-Free Survival in Endometrial Stromal Sarcomas: A...

Endometrial stromal tumors (ESTs) represent a heterogeneous group of uterine mesenchymal neoplasms with variable clinical outcomes. Although histological grading is a cornerstone for prognosis, the contribution of proliferative and immune microenvironment markers remains incompletely defined.

We retrospectively analyzed 90 patients diagnosed with endometrial stromal nodule (ESN) (n = 30), low-grade endometrial stromal sarcoma (LG-ESS, n = 30), and high-grade endometrial stromal sarcoma (HG-ESS, n = 30) between 2017 and 2025 across 35 public and private clinics in four Georgian cities. All specimens underwent standardized immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), Ki67, cyclinD1, cyclin-dependent kinase 4 (CDK4), CD117, forkhead box P3 (FOXP3), CD163, and CD34. Disease-free survival (DFS) was calculated from date of surgery to recurrence/metastasis. Kaplan-Meier curves and log-rank tests were used to assess survival differences, and data-driven cutoffs (Youden index) were employed to stratify biomarker expression. Multivariable Cox proportional hazards regression was applied to identify independent predictors of recurrence.

Median follow-up was 55 months. DFS significantly differed by histology: not reached for ESN, 20.0 months for LG-ESS, and 5.0 months for HG-ESS (log-rank P < 0.0001). High Ki67, cyclinD1, CDK4, CD117, FOXP3, and CD163 predicted shortened DFS, while ER/PR expression correlated with prolonged DFS (all P < 0.0001). In adjusted models, lymphovascular space invasion (LVSI) (odds ratio (OR): 3.59, 95% confidence interval (CI): 3.21 - 3.87), Ki67 (OR: 4.65, 4.08 - 5.10), tumor necrosis (OR: 2.39, 2.06 - 2.79), cyclinD1 (OR: 2.20, 1.99 - 2.43), and CD163 (OR: 2.06, 1.72 - 2.51) remained independently associated with recurrence.

Beyond histological grade, proliferative signaling and M2 macrophage polarization strongly influence recurrence risk in ESS. These findings highlight potential diagnostic and therapeutic targets, suggesting integration of immune and cell-cycle biomarkers into future risk stratification models.