Diagnostic Performance of Galectin-1 and Mucin-1 in Uterine Tumors: A Case–Control Study

Background and Objectives: Uterine leiomyomas are common benign tumors, whereas uterine sarcomas are rare but aggressive malignancies. Preoperative differentiation among leiomyoma, smooth muscle tumor of uncertain malignant potential (STUMP), and uterine sarcoma remains a major clinical challenge, with diagnosis often established only after histopathological evaluation. The identification of reliable circulating biomarkers could improve preoperative risk stratification and guide surgical decision-making. This study aimed to evaluate the usefulness of galectin-1 and mucin-1 in the diagnosis of uterine tumors. Materials and methods: This prospective, single-center case–control study was conducted at the Third Department of Obstetrics & Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, between 2013 and 2024. Serum galectin-1 and mucin-1 levels were measured preoperatively using ELISA and electrochemiluminescence immunoassay (ECLIA), respectively. Group comparisons were performed using non-parametric tests. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Multivariable logistic regression was used to assess independent associations with sarcomas/STUMP status. Results: The study population comprised 156 women (49 healthy controls, 90 patients with uterine myomas, 8 with STUMP and 9 patients with uterine sarcomas) treated during the study period. Galectin-1 differed significantly across the four histological groups (p < 0.001), with higher concentrations in uterine sarcoma than in healthy controls (p < 0.001) and leiomyoma (p = 0.002). MUC1 also differed overall (p = 0.031), with higher concentrations in uterine sarcoma than in leiomyoma (adjusted p = 0.031). In the primary leiomyoma versus sarcoma/STUMP ROC analysis, galectin-1 showed modest discrimination (AUC 0.693, 95% CI 0.559–0.826), while MUC1 showed weaker discrimination (AUC 0.618, 95% CI 0.468–0.768). Conclusions: Serum galectin-1 may have potential as an adjunctive biomarker in the preoperative assessment of uterine tumors, but its modest discrimination and unstable cutoff-dependent performance may preclude its use as a standalone diagnostic test. MUC1 showed limited diagnostic utility in the primary clinical comparison. Given the clinical implications of misdiagnosis, particularly regarding surgical management, further validation in larger cohorts and multimarker approaches are warranted.