MSI testing : What's new? What should be considered?

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Genomics

Background:

• Immune checkpoint inhibitors (ICIs) show efficacy in treating cancers with high-grade microsatellite instability (MSI-H) or deficient mismatch repair protein (dMMR).
• Recent approvals of PD-1 inhibitors (e.g., pembrolizumab) for advanced dMMR/MSI-H colorectal cancer and endometrial carcinoma highlight the clinical significance of these biomarkers.
• Optimal diagnostic testing strategies for MSI-H/dMMR are needed to guide treatment decisions.

Purpose of the Study:

• To re-evaluate the optimal testing methods for MSI-H/dMMR in routine diagnostics.
• To propose a quality-assured, reliable, and cost-effective testing algorithm for MSI-H/dMMR detection.
• To facilitate early consideration of predictive, prognostic, and predispositional implications of MSI-H/dMMR status for patient counseling and treatment planning.

Main Methods:

• Evaluation of the strengths and weaknesses of widely available diagnostic methods: immunohistochemistry (IHC) and polymerase chain reaction (PCR).
• Development of a proposed test algorithm for dMMR/MSI-H detection.
• Alignment of testing recommendations with international guidelines (NICE, NCCN) for colorectal cancer (CRC) and endometrial carcinoma (EC).

Main Results:

• A new testing algorithm enables quality-assured, reliable, and cost-effective dMMR/MSI-H detection.
• Testing is feasible at the primary diagnosis stage for CRC and EC, aligning with international recommendations.
• Clinicians can utilize MSI-H/dMMR test results for comprehensive patient counseling and treatment strategy formulation.

Conclusions:

• The proposed algorithm supports routine, high-quality dMMR/MSI-H testing for optimizing ICI therapy selection.
• Early detection of dMMR/MSI-H status in CRC and EC is critical for personalized cancer care.
• Participation in interlaboratory comparisons and continuous data documentation are recommended for quality assurance.