Comparative Analysis of Cyclin E1 Expression in Uterine Leiomyosarcomas and Leiomyomas.

Background/Objectives: Uterine leiomyosarcoma (uLMS) shares clinical and radiological similarities with benign uterine leiomyoma (LM), while validated discriminatory markers remain scarce. We compared cyclin E1 (CCNE1) expression in uLMS and LM tissue samples. Methods: This retrospective case-control study included 61 patients (16 uLMS, 45 LM) treated at a single institution (2017-2023). Of 22 eligible uLMS cases, six were excluded because suitable tissue was unavailable and they had significantly higher FIGO stages than the included cases. CCNE1 immunoreactivity was assessed using an adapted Allred score in five non-overlapping high-power fields selected from regions of highest expression. Two blinded pathologists independently scored each field, and the patient-level median was used for primary analysis. Results: The median CCNE1 Allred score was 6 (IQR 5-6) in uLMS versus 2 (IQR 0-3) in LM (p < 0.001), with excellent interobserver agreement (ICC 0.94). The AUC was 0.941 (95% CI 0.875-0.990). A data-derived cut-off ≥4 yielded 93.8% sensitivity and 84.4% specificity. A conservative minimum-expression analysis yielded an AUC of 0.882. Postmenopausal status was strongly associated with uLMS but was nearly completely confounded with the diagnostic group (12/16 uLMS vs. 0/45 LM). A premenopausal-only analysis was directionally consistent but underpowered. Clinical symptoms and tumor size did not differ between the groups. Conclusions: CCNE1 immunoexpression was substantially higher in uLMS than LM, with excellent reproducibility. Diagnostic-performance estimates remain exploratory and were influenced by tumor-region sampling, menopausal imbalance, and under-representation of advanced-stage uLMS. Independent multicenter validation, particularly in premenopausal and advanced-stage disease, is required before clinical application.