[MSI testing : What is new? What should be considered? German version].

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Therapeutics

Background:

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

Purpose of the Study:

• To re-evaluate optimal testing strategies for dMMR/MSI-H in routine diagnostics.
• To propose a quality-assured, reliable, and cost-effective testing algorithm for dMMR/MSI-H.
• To facilitate early consideration of predictive, prognostic, and predispositional implications of dMMR/MSI-H testing.

Main Methods:

• Evaluation of strengths and weaknesses of immunohistochemistry (IHC) and polymerase chain reaction (PCR) methods.
• Development of a proposed test algorithm for dMMR/MSI-H detection.
• Consideration of international recommendations (NICE, NCCN) for testing in primary diagnosis.

Main Results:

• A new test algorithm enables quality-assured, reliable, and cost-effective dMMR/MSI-H testing.
• Testing is feasible at the primary diagnosis stage for colorectal and endometrial cancers.
• Clinicians can utilize test results for patient counseling and treatment recommendations from the outset.

Conclusions:

• The proposed algorithm supports routine dMMR/MSI-H testing for guiding ICI therapy.
• Early and accurate dMMR/MSI-H detection impacts patient management and treatment selection.
• Quality assurance through interlaboratory comparisons and result documentation is strongly recommended.