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Biomolecules
Volume 15
Issue 10
10.3390/biom15101370
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Traditional and New Views on MSI-H/dMMR Endometrial Cancer

by
Chuqi Liu
1,2,†,
Huiyu Ping
1,2,†,
Mengmeng Yao
1,2,
Xinru Li
1,3,
Qingxin Li
1,2,
Ruotong Hu
1,2,
Yawen Xu
1,3,
Kaidi Meng
4,
Fei Gao
1,5,* and
Kai Meng
1,*
1
Lin He’s Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining 272067, China
2
College of Clinical Medicine, Jining Medical University, Jining 272067, China
3
College of Medical Imaging and Laboratory Medicine, Jining Medical University, Jining 272067, China
4
College of Medical Laboratory, Qilu Medical University, Zibo 255300, China
5
Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2025, 15(10), 1370; https://doi.org/10.3390/biom15101370
Submission received: 19 June 2025 / Revised: 19 September 2025 / Accepted: 25 September 2025 / Published: 26 September 2025
(This article belongs to the Special Issue Human Reproductive Biology: Uncertainties and Controversies)
Versions Notes

Abstract

MSI-H/dMMR endometrial cancer (EC) is closely linked to the mismatch repair (MMR) pathway, and its pathogenesis is associated with microsatellite instability (MSI) caused by abnormalities in the core genes of the conventional MMR system. This cancer exhibits a distinct immune microenvironment, which makes it suitable for treatment with immune checkpoint inhibitors (ICIs). This cancer type demonstrates heterogeneity, encompassing Lynch syndrome (LS)-associated EC (characterized by germline mutations), sporadic EC (attributed to MLH1 promoter hypermethylation), and Lynch-like EC (driven by somatic mutations). Research indicates that these three dMMR EC subtypes possess different immune microenvironments, which may influence the therapeutic efficacy of ICIs. However, the impact of somatic mutations in traditional MMR genes on EC has often been overlooked. Furthermore, over 50% of patients with MSI exhibit no response to ICIs, potentially due to abnormalities in nontraditional MMR genes. This review discusses the role of traditional and nontraditional MMR genes in dMMR EC and related treatment strategies, highlights key issues in the current diagnosis and treatment of dMMR EC, and aims to enhance understanding of its heterogeneity and advance precision diagnosis and treatment.
Keywords: MSI-H/dMMR endometrial cancer; base mismatch repair pathway; next-generation sequencing MSI-H/dMMR endometrial cancer; base mismatch repair pathway; next-generation sequencing

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MDPI and ACS Style

Liu, C.; Ping, H.; Yao, M.; Li, X.; Li, Q.; Hu, R.; Xu, Y.; Meng, K.; Gao, F.; Meng, K. Traditional and New Views on MSI-H/dMMR Endometrial Cancer. Biomolecules 2025, 15, 1370. https://doi.org/10.3390/biom15101370

AMA Style

Liu C, Ping H, Yao M, Li X, Li Q, Hu R, Xu Y, Meng K, Gao F, Meng K. Traditional and New Views on MSI-H/dMMR Endometrial Cancer. Biomolecules. 2025; 15(10):1370. https://doi.org/10.3390/biom15101370

Chicago/Turabian Style

Liu, Chuqi, Huiyu Ping, Mengmeng Yao, Xinru Li, Qingxin Li, Ruotong Hu, Yawen Xu, Kaidi Meng, Fei Gao, and Kai Meng. 2025. "Traditional and New Views on MSI-H/dMMR Endometrial Cancer" Biomolecules 15, no. 10: 1370. https://doi.org/10.3390/biom15101370

APA Style

Liu, C., Ping, H., Yao, M., Li, X., Li, Q., Hu, R., Xu, Y., Meng, K., Gao, F., & Meng, K. (2025). Traditional and New Views on MSI-H/dMMR Endometrial Cancer. Biomolecules, 15(10), 1370. https://doi.org/10.3390/biom15101370

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