ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Microsatellite Instability-High Endometrial Cancers with MLH1 Promoter Hypermethylation Have Distinct Molecular and Clinical Profiles.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Efficacy and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a meta-analysis with trial sequential analysis of randomized controlled trials.Frontiers in immunology · 2025Pooled it
- Effectiveness and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a systematic review and meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study.Nature communications · 2026Trial
- Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.Nature medicine · 2024Trial
- Dedifferentiation in endometrial cancer is associated with HLA-I silencing that may be restored by IFN-γ.The Journal of pathology · 2026Article
- Breaking barriers in gynecologic malignancies with adoptive cell transfers and nanomedicine.Cell biomaterials · 2026Article
- The role of non-coding variants in hereditary cancer syndromes: mechanistic insights and clinical implications.Annals of medicine and surgery (2012) · 2026Review
- Analysis of DNA mismatch repair and microsatellite instability in molecular typing of endometrial carcinoma.Discover oncology · 2026Article
- Loss of Ribosomal Protein L22 (RPL22) Expression Identifies a Transcriptional Subset of MLH1-Deficient Endometrial Cancers With Lower Numbers of Tumor-Associated Lymphocytes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Predictive biomarkers of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.Therapeutic advances in medical oncology · 2026Review
- Predictive biomarkers for immunotherapy response in endometrial cancer: current insights and future directions.Exploration of targeted anti-tumor therapy · 2026Review
- CircCLMP Suppresses Anti-Tumor Immunity by Inhibiting Activation of IRF3 and Interferon Response in Microsatellite Instability-high Endometrial Cancer.International journal of biological sciences · 2026Article
- Molecular analysis of the evolutionary history of endometrial and ovarian carcinoma in Lynch syndrome.International journal of cancer · 2025Article
- DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.Cancer science · 2025Review
- Epigenetic Factors in Pathogenesis of Retinoblastoma: DNA Methylation and Histone Acetylation.Current issues in molecular biology · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- The protective role of γδ T cells in endometrial cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Traditional and New Views on MSI-H/dMMR Endometrial Cancer.Biomolecules · 2025Review
- A working group report from the 2024 National Cancer Institute / Gynecologic Cancer Steering Committee endometrial cancer clinical trials planning meeting: refining the approach to endometrial cancer in the immunotherapy era.Journal of the National Cancer Institute · 2025Article
- EPM2 AIP1 immunohistochemistry as a surrogate of promoter methylation analysis in endometrial carcinoma.Virchows Archiv : an international journal of pathology · 2025Article
Corrections and comments
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Authors and funding
23 authors at 1 institution in 1 country.
Funding
Abstract
purposeMicrosatellite instability-high (MSI-H) endometrial carcinomas are underpinned by distinct mechanisms of DNA mismatch repair deficiency (MMR-D). We sought to characterize the clinical and genetic features of MSI-H endometrial cancers harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph). EXPERIMENTAL
designOf > 1,100 patients with endometrial cancer that underwent clinical tumor-normal sequencing, 184 had MSI-H endometrial cancers due to somatic MMR mutations or MLH1ph, or harbored pathogenic germline MMR mutations. Clinicopathologic features, mutational landscape, and tumor-infiltrating lymphocyte (TIL) scores were compared among MMR-D groups using nonparametric tests. Log-rank tests were used for categorical associations; Kaplan-Meier method and Wald test based on Cox proportional hazards models were employed for continuous variables and survival analyses.
resultsCompared with patients with germline (n = 25) and somatic (n = 39) mutations, patients with MLH1ph endometrial cancers (n = 120) were older (P < 0.001), more obese (P = 0.001) and had more advanced disease at diagnosis (P = 0.025). MLH1ph endometrial cancers were enriched for JAK1 somatic mutations as opposed to germline MMR-D endometrial cancers which showed enrichment for pathogenic ERBB2 mutations. MLH1ph endometrial cancers exhibited lower tumor mutational burden and TIL scores compared with endometrial cancers harboring germline or somatic MMR mutations (P < 0.01). MLH1ph endometrial cancer patients had shorter progression-free survival (PFS) on univariate analysis, but in multivariable models, stage at diagnosis remained the only predictor of survival. For stage I/II endometrial cancer, two-year PFS was inferior for patients with MLH1ph endometrial cancers compared with germline and somatic MMR groups (70% vs. 100%, respectively).
conclusionsMLH1ph endometrial cancers likely constitute a distinct clinicopathologic entity compared with germline and somatic MMR-D ECs with potential treatment implications.
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