The Role of CA125 and HE4 in Uterine Sarcomas: Beyond Diagnosis and Prognosis-A Systematic Review and Case Series from a Single Institution.

: Serum biomarkers such as Carcinoma Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are widely used in the diagnosis and prognosis of gynecological malignancies. Serum biomarkers such as CA125 and HE4 represent essential tools in improving early detection, risk stratification, and therapeutic decision-making for gynecological malignancies. However, their role in identifying uterine sarcomas remains debated. This systematic review and case series aims to examine the diagnostic and prognostic significance of CA125 and HE4 in uterine sarcomas. : A systematic review was performed on studies investigating serum CA125 and HE4 levels in uterine sarcomas. A case series of all uterine sarcomas treated at the Campus Bio-Medico Gynecology Unit of Rome from 2010 to 2020 was analyzed. : The analysis of the 11 selected studies allowed us to investigate the role of CA125 in uterine sarcomas. No studies analyzing the role of HE4 in monitoring the disease were found. A total of 16 patients with confirmed uterine leiomyosarcoma were included in our case series. : Neither CA125 nor HE4 can currently be considered definitive biomarkers for the diagnosis of uterine leiomyosarcomas. However, they may serve as useful adjuncts in the differential diagnosis between leiomyomas and leiomyosarcomas, particularly in reproductive-age patients.