ArticleGynecologic oncology2025
Molecular characteristics by race and ethnicity of patients with high tumor mutational burden, high microsatellite instability, and mismatch repair deficiency: Real-world data from the multi-institutional Endometrial cancer Molecularly Targeted Therapy Consortium (ECMT2).
Article in Gynecologic oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveMismatch repair deficiency (dMMR), high microsatellite instability (MSI-H), and high tumor mutation burden (TMB-H) are predictive and prognostic biomarkers in endometrial cancer. We aimed to characterize the racial/ethnic distribution of molecular markers and the clinical characteristics among endometrial cancer patients with TMB-H and MSI-H/dMMR.
methodsThe Endometrial Cancer Molecularly Targeted Therapy Consortium is a centrally verified clinical and molecular repository. Patients with endometrial cancer who underwent tumor profiling were included. TMB-H was defined as ≥10-12 mutations per megabase. MSI-H was determined by next-generation sequencing or polymerase chain reaction, and dMMR by loss of MLH1, MSH2, MSH6, or PMS2 on immunohistochemistry. Tumor biomarker positivity was defined as TMB-H and/or MSI-H/dMMR. Overall survival was assessed using Kaplan-Meier and Cox proportional hazard models.
resultsAmong 742 patients, 22 % (n = 164) were biomarker positive: 12 % (n = 87) had both TMB-H and MSI-H/dMMR, 8 % (n = 63) had MSI-H/dMMR alone, and 2 % (n = 14) had 14 TMB-H alone. Only 9 % of non-Hispanic Black patients had biomarker positive tumors compared to 26 % of patients from other racial/ethnic groups. Pathogenic POLE mutations were rare (<1 %, n = 5). Patients with TMB-H had a higher proportion of high-risk histologies (43 %) than those with MSI-H/dMMR (24 %). Biomarker positive tumors were associated with a lower risk of death compared to biomarker negative tumors (aHR 0.63, 95 % CI: 0.46, 0.88).
conclusionLess than 10 % of non-Hispanic Black patients with endometrial cancer had TMB-H and/or MSI-H/dMMR, and biomarker positivity was associated with improved survival. Prospective studies are necessary to elucidate how these molecular differences impact treatment and outcomes.
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