[Testing deficient mismatch repair and microsatellite instability : A focused update. German version]

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Research

Context:

• Mismatch repair deficiency (dMMR) and high-grade microsatellite instability (MSI-H) testing are essential in routine colorectal cancer (CRC) diagnostics.
• Initially linked to hereditary cancer predisposition (Lynch syndrome), MSI testing is now pivotal for predicting response to immune checkpoint inhibitors (ICIs).
• The expanding use of ICIs in various cancers beyond CRC necessitates updated dMMR/MSI testing guidelines.

Purpose:

• To provide an updated review of dMMR/MSI testing methodologies and their clinical applications.
• To address the challenges in interpreting immunohistochemical (IHC) stains and highlight the utility of PCR-based methods.
• To offer a practical flowchart for diagnostic decision-making, incorporating new data on discordant results and the role of Next-Generation Sequencing (NGS).

Summary:

• The review focuses on the evolving landscape of dMMR/MSI testing, particularly for ICI therapy selection across multiple cancer types.
• It evaluates the strengths and limitations of immunohistochemistry (IHC) and PCR-based assays, discussing discordances between these methods.
• The paper emphasizes the importance of robust quality assurance measures, including proficiency testing and continuous education, for accurate dMMR/MSI assessment.

Impact:

• This work supports clinicians and pathologists in making informed decisions regarding dMMR/MSI testing for cancer patients.
• It facilitates the optimal use of immune checkpoint inhibitors by improving the accuracy of predictive biomarker assessment.
• The updated guidance and diagnostic flowchart aim to enhance patient care and treatment outcomes in oncology.