Endometrial mesonephric-like adenocarcinoma: Clinicopathologic features, treatment, and outcomes

Shuping Yan; Yanpeng Tian; Mingyue Li; Xiaonan Wang; Jiayi Wang; Kuisheng Chen; Tianjiao Lai; Ye Zhang; Xixaoxiao Zhang; Yana Liu; Yuxi Jin; Xueyan Liu; Meng Mao; Qian Wang; Ruixia Guo

doi:10.17305/bb.2025.12993

Authors

Shuping Yan Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Yanpeng Tian Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China https://orcid.org/0000-0001-8049-1281
Mingyue Li Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Xiaonan Wang Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Jiayi Wang Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Kuisheng Chen Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Tianjiao Lai Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Ye Zhang Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Xixaoxiao Zhang Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Yana Liu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Yuxi Jin Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Xueyan Liu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Meng Mao Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Qian Wang Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Ruixia Guo Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

DOI:

https://doi.org/10.17305/bb.2025.12993

Keywords:

Uterine cancer, mesonephric-like adenocarcinoma, clinicopathological features, prognosis, retrospective analysis, KRAS mutation

Abstract

Endometrial mesonephric-like adenocarcinoma (MLA) is a rare subtype of uterine corpus endometrial carcinoma (UCEC) first described in 2016. The clinicopathological features, treatment options, and prognosis of endometrial MLA remain poorly understood. In this study, we retrospectively analyzed the clinicopathological characteristics, molecular features, treatment regimens, and outcomes of 11 patients diagnosed with endometrial MLA. The most prevalent symptom observed was postmenopausal bleeding. Notably, 78% (7 out of 9) of patients were diagnosed at advanced FIGO stages (II-IV), with four cases presenting with distant metastasis upon initial examination. Multivisceral metastases were identified in three cases, with lung metastases being the most common, occurring in 45% of patients. The median progression-free survival (PFS) was 16 months (95% confidence intervals: 6-26). All tumors tested negative for progesterone receptors (PR), while 91% of patients (10 out of 11) were negative for estrogen receptors (ER). Most patients exhibited positive immunohistochemical staining for "mesonephric-like" markers, including GATA-binding protein 3 (GATA-3), thyroid transcription factor-1 (TTF-1), and CD10. Furthermore, 91% of patients showed a wild-type p53 immunostaining pattern. Among the 11 patients, five underwent KRAS mutation testing, revealing KRAS mutations in all tested individuals (p.G12D in 2/5, p.G12A in 1/5, p.G12V in 1/5, and p.G13D in 1/5). These findings indicate that 78% of endometrial MLA patients were diagnosed at an advanced stage and suggest that this subtype may exhibit more aggressive behavior compared to endometrial endometrioid carcinoma. The consistent presence of KRAS mutations in patients who underwent testing highlights the potential role of KRAS in the initiation and progression of endometrial MLA, positioning it as a promising therapeutic target.