[Synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC): clinicopathological and molecular features]

Objective: To investigate the clinicopathological characteristics and molecular features of synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC). Methods: A total of 28 patients diagnosed with SEO-EC at the Peking University Third Hospital, Hunan Cancer Hospital and Peking University People's Hospital between September 2016 and July 2023 were included retrospectively. Next-generation sequencing (NGS) was performed to assess the clonal relatedness of 28 paired endometrial and ovarian tumors. Extra-uterine-ovarian disease specimens in four patients diagnosed with SEO-EC were further tested with comprehensive NGS analysis. Normal tissue/blood samples of 27 patients were available for NGS analysis. All cases were classified according to WHO 2020 histologic criteria and FIGO 2023 staging system. Relevant clinicopathological features were also analyzed. Results: The age of 28 patients was (47.3±8.5)years. Most patients (85.7%, 24/28) were premenopausal. In most instances, ovarian and endometrial carcinomas exhibited consistent morphology (82.1%, 23/28) as well as molecular subtypes (96.4%, 27/28). NGS confirmed a clonal relationship in all cases. The most common somatic mutations shared between endometrial and ovarian tumors were PTEN (64.3%, 18/28), PIK3CA (46.4%, 13/28), ARID1A (28.6%, 8/28), CTNNB1 (25.0%, 7/28), and KRAS (21.4%, 6/28). A majority of patients (82.1%, 23/28) exhibited a favorable prognosis, with only 5 patients identified as the WHO high-risk group and FIGO advanced-stage experiencing recurrence and tumor-specific death. In addition, 22.2% (6/27) of patients carried pathogenic germline mutations. Conclusions: In this study, there is a high degree of concordance between the histologic and molecular subtypes of the endometrial and ovarian tumors in SEO-EC. We confirmed a clonal relationship in all tested paired SEO-EC. Patients identified as the WHO high-risk group and advanced FIGO stages may exhibit a poor prognosis in SEO-EC.