Mismatch Repair Deficiency Profiling and Its Impact on Management and Prognosis in Endometrial Cancer Patients: A...

With an increasing incidence, endometrial cancer (EC) is the most prevalent gynecologic cancer in developed countries. Although histological classification has been used traditionally, its usage in forecasting clinical behavior was less effective. A molecular classification of EC has been introduced by the Cancer Genome Atlas (TCGA), which has separated it into four subgroups: p53-abnormal (p53abn), mismatch repair deficiency (MMRd), polymerase epsilon (POLE)-mutated (POLEmut), and no specific molecular profile (NSMP). The prognostic value of this molecular subtyping is superior. This narrative review analyzes the clinicopathological features of MMRd tumors, highlighting their intermediate prognosis relative to other molecular subtypes, while also noting associations with high-grade, lymphovascular space invasion, and lymph node metastasis. For this purpose, relevant studies were retrieved from PubMed, Scopus, and Web of Science up to 2025, focusing on clinicopathological correlations and treatment outcomes. Furthermore, we analyze the important therapeutic implications of MMR status. About 25%-30% of cases are classified as MMRd EC and are associated with an intermediate prognosis. The increased mutational burden in MMRd tumors enhances their susceptibility to immune checkpoint inhibitors such as pembrolizumab and dostarlimab, which have demonstrated considerable efficacy and altered the treatment approach for patients with advanced or recurrent MMRd EC. This review highlights the significance of MMR testing in risk stratification, prognosis, and planning of personalized treatment, ultimately improving patient outcomes.