Microsatellite Instability Status and Mismatch Repair Defects Testing in Endometrial Cancer—Insights from the Multicenter E-PEC Trial

<b>Background:</b> Mismatch repair (MMR) and microsatellite instability (MSI) testing have become essential biomarkers in the molecular classification of endometrial cancer (EC), guiding adjuvant treatment decisions and eligibility for immune checkpoint inhibition. Although international guidelines recommend universal testing, real-world implementation remains heterogeneous. This study aimed to evaluate trends in MMR and MSI testing and associated molecular diagnostics in Germany between 2018 and 2022. <b>Methods:</b> A retrospective multicenter analysis was conducted across German tertiary care centers. Data from patients with histologically confirmed EC between 2018 and 2022 were extracted from standardized electronic pathology records. Annual testing rates for <i>MSI</i>, <i>MMR</i>, <i>POLE</i>, <i>TP53</i>, and L1CAM were analyzed using descriptive statistics and trend analysis (Chi-square test for trend, <i>p</i> < 0.05). Therapeutic data were collected to assess the use of immune checkpoint inhibitors. <b>Results:</b> There was a significant increase in the annual rates of molecular testing for MSI, <i>POLE</i>, <i>TP53</i>, and L1CAM over the five-year observation period (all <i>p</i> < 0.05). TP53 testing showed the highest increase (13.1% → 78.6%), while MSI testing rose from 82.9% to 97.4%. Both <i>POLE</i> and L1CAM testing were virtually absent in 2018 (0% and 1.6%) but reached 15.7% by 2022. <b>Conclusions:</b> This study demonstrates a rapid and substantial implementation of MMR and MSI testing in German clinical practice, reflecting successful translation of trial results into routine care. However, implementation of testing in guidelines appeared time-shifted. For bridging this gap, annual guideline updates seem to be necessary.