Molecular classification and fertility-sparing outcomes in endometrial cancer and atypical endometrial hyperplasia

Jiayi Wang; Guozhong Jiang; Shuping Yan; Yanpeng Tian; Yuxi Jin; Hanlin Fu; Lulu Si; Mingbo Cai; Xueyan Liu; Ruixia Guo

doi:10.17305/bb.2025.12445

Authors

Jiayi Wang Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China
Guozhong Jiang Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Shuping Yan Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Yanpeng Tian Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China https://orcid.org/0000-0001-8049-1281
Yuxi Jin Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China
Hanlin Fu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China
Lulu Si Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China
Mingbo Cai Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China
Xueyan Liu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China
Ruixia Guo Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, China

DOI:

https://doi.org/10.17305/bb.2025.12445

Keywords:

Endometrial cancer, EC, atypical endometrial hyperplasia, AEH, fertility-preserving treatment, molecular classification, fertility outcomes

Abstract

Molecular classification has emerged as a critical tool for guiding personalized treatment in endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). This retrospective study aimed to assess the impact of molecular classification on fertility-sparing treatment outcomes in patients diagnosed with EC and AEH who underwent fertility preservation therapy between 2006 and 2021. Patients were categorized into four molecular subtypes using immunohistochemistry (IHC) and Sanger sequencing, based on the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE): POLE-ultramutated, mismatch repair (MMR) deficient (MMRd), p53 abnormal (p53abn), and p53 wild-type (p53wt). All patients were evaluated for oncological prognosis and fertility outcomes, with a total of 103 patients included in the analysis. Recurrence rates exhibited significant differences among the molecular classifications, with the lowest recurrence rate observed in the p53wt subtype (19.7%), followed by MMRd (30.4%), POLE-ultramutated (66.7%), and p53abn (71.4%) subtypes. Multivariate Cox regression analysis indicated that the p53abn subtype was a significant risk factor for recurrence following conservation therapy when compared to the p53wt subtype. Additionally, there was a notable disparity in standard surgical treatment due to treatment failure, with operation rates of 7.5%, 19.2%, 66.7%, and 57.1% for the p53wt, MMRd, POLE-ultramutated, and p53abn subtypes, respectively. Regarding fertility outcomes, the p53wt group demonstrated the highest pregnancy rate after achieving a complete response compared to the other subtypes; however, no significant differences were observed in overall pregnancy outcomes. The ProMisE molecular classification holds significant prognostic value for patients with EC and AEH undergoing fertility-sparing treatment. Among the molecular subtypes, p53wt appears to be the most favorable for fertility-preserving interventions. This study provides essential insights into reproductive outcomes for this patient population.