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

**Authors:** Büsra Eser, David Papior, Jon Salmanton-García, Oliver A. Cornely, Bernd Morgenstern, Clarissa Herpel, Julia C. Radosa, Anas Almuheimid, Bahriye Aktas, Laura Weydandt, Julia Wittenborn, Philipp Meyer-Wilmes, Verena Friebe, Christiane Leidinger, Rainer Kimmig, Fabinshy Thangarajah

PMC · DOI: 10.3390/diagnostics16010100 · Diagnostics · 2025-12-27

## TL;DR

This study shows how testing for MMR and MSI in endometrial cancer improved in Germany from 2018 to 2022, with some tests increasing significantly over time.

## Contribution

The study provides real-world insights into the implementation of molecular testing for endometrial cancer in Germany.

## Key findings

- MSI testing rates increased from 82.9% to 97.4% between 2018 and 2022.
- TP53 testing rates rose from 13.1% to 78.6% over the same period.
- POLE and L1CAM testing, nearly absent in 2018, reached 15.7% by 2022.

## Abstract

Background: 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. Methods: 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 MSI, MMR, POLE, TP53, and L1CAM were analyzed using descriptive statistics and trend analysis (Chi-square test for trend, p < 0.05). Therapeutic data were collected to assess the use of immune checkpoint inhibitors. Results: There was a significant increase in the annual rates of molecular testing for MSI, POLE, TP53, and L1CAM over the five-year observation period (all p < 0.05). TP53 testing showed the highest increase (13.1% → 78.6%), while MSI testing rose from 82.9% to 97.4%. Both POLE and L1CAM testing were virtually absent in 2018 (0% and 1.6%) but reached 15.7% by 2022. Conclusions: 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.

## Linked entities

- **Genes:** POLE (DNA polymerase epsilon, catalytic subunit) [NCBI Gene 5426], TP53 (tumor protein p53) [NCBI Gene 7157], L1CAM (L1 cell adhesion molecule) [NCBI Gene 3897]
- **Proteins:** MRC1 (mannose receptor C-type 1)
- **Diseases:** endometrial cancer (MONDO:0002447)

## Full-text entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, L1CAM (L1 cell adhesion molecule) [NCBI Gene 3897] {aka CAML1, CD171, HSAS, HSAS1, HYCX, MASA}
- **Diseases:** EC (MESH:D016889)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12786114/full.md

## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12786114/full.md

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Source: https://tomesphere.com/paper/PMC12786114