EMQN best practice guidelines for analysis and reporting of microsatellite instability in solid tumours

Microsatellite instability (MSI) represents the progressive and measurable accumulation of insertion and deletion variants within short tandem repeat DNA sequences throughout the genome. Prior research has shown that high levels of MSI typically occur following the loss of function within the DNA mismatch repair (MMR) system, which normally corrects replication errors. This MMR deficiency serves as a critical cancer biomarker linked to chemotherapy resistance and favorable responses to immune checkpoint blockade therapies. The presence of these genetic alterations is a hallmark of Lynch syndrome, which remains one of the most prevalent hereditary cancer syndromes identified in clinical practice. Over the past two decades, the biological understanding of these mechanisms and the associated testing methodologies have undergone rapid expansion across the scientific community. Despite these advancements, the field lacked unified standards for the clinical interpretation and reporting of MSI results across different laboratory settings. This absence of evidence motivated the development of comprehensive best practice guidelines to ensure diagnostic accuracy and clinical utility for patients with solid tumors.

This project establishes 15 best practice recommendations for the analysis and reporting of microsatellite instability in solid tumors to harmonize global diagnostic efforts. The initiative addresses the urgent need for up-to-date guidance following rapid developments in MSI testing methods and their expanding clinical implications. Researchers sought to standardize technical aspects of testing to minimize variability between diagnostic laboratories and improve the reproducibility of results. The study also focuses on refining the clinical interpretation of results specifically for Lynch syndrome screening to identify at-risk families more effectively. Another primary objective involves optimizing the reporting of MSI status to guide the administration of immune checkpoint blockade therapy in patients with advanced malignancies. By providing example report wording, the authors aim to assist in the practical implementation of these standards within busy clinical environments. The overall goal is to provide a robust framework for genomic scientists, clinicians, and academics involved in the complex landscape of oncological diagnostics.

An expert working group conducted an extensive review of existing literature to identify current challenges and evidence-based solutions regarding microsatellite instability. This group devised a preliminary set of 15 recommendations covering both technical and clinical domains to address the multifaceted nature of MSI testing. The proposed guidelines underwent a rigorous finalization process through consultation with clinical and laboratory scientists across multiple international jurisdictions. These partners were affiliated with the European Molecular Genetics Quality Network (EMQN) to ensure broad professional consensus and high-quality standards. The methodological framework categorized the guidance into seven technical recommendations and eight clinical interpretation recommendations to provide a clear structure for users. Discussions within the working group also addressed common terminology and various MSI analysis methods currently in use to resolve existing nomenclature conflicts. This collaborative approach ensured that the final guidelines reflected the practical realities and technical constraints of modern diagnostic testing laboratories.

The study produced 15 finalized best practice recommendations that address the full spectrum of MSI testing and reporting for solid tumor analysis. Seven specific recommendations focus on the key technical aspects required for accurate microsatellite instability analysis, including sample preparation and assay selection. Eight additional recommendations provide a structured approach for the clinical interpretation of MSI data in a diagnostic context to ensure patient safety. These clinical guidelines emphasize the identification of Lynch syndrome and the selection of patients for immune checkpoint blockade based on MMR status. The results include standardized example report wording designed to facilitate immediate implementation and promote consistency across different healthcare systems. The consensus process clarified common terminology to reduce ambiguity in scientific communication between laboratory scientists and treating physicians. These outputs provide a definitive reference for genomic scientists working within the constraints of modern diagnostic environments to deliver precise results.

These guidelines provide a necessary foundation for the standardization of MSI testing across global diagnostic networks and clinical research organizations. Implementing these recommendations will likely improve the reliability of Lynch syndrome screening and the precision of immunotherapy patient selection. The authors anticipate that the provided reporting templates will reduce errors and inconsistencies in clinical documentation across various laboratory settings. Future research and clinical practice will benefit from the unified terminology and methodological clarity established in this consensus work. The guidelines serve as a vital resource for clinicians and academics seeking to understand the complexities of MMR deficiency in solid tumors. Continued adherence to these best practices will ensure that MSI analysis remains a robust and trustworthy tool in the era of precision oncology. The study concludes that standardized reporting is essential for the effective management and treatment planning of patients with MSI-high solid tumors.