Routine use of MSI testing in colorectal cancer using a proposed algorithm

Area of Science:

• Oncology
• Molecular Diagnostics
• Gastroenterology

Background:

• Defects in the mismatch repair system (dMMR) are present in 15% of colorectal cancers.
• MMR status is crucial for identifying Lynch Syndrome (LS), determining prognosis, and guiding treatment decisions.
• Immunohistochemistry (IHC) and microsatellite instability (MSI) analysis via PCR are standard methods for MMR status determination.

Purpose of the Study:

• To evaluate the performance of the Idylla™ MSI assay as an alternative to IHC for dMMR detection in colorectal cancer.
• To assess the utility and applicability of a newly introduced decision algorithm for MMR status determination.
• To investigate the occurrence of false-positive results with the Idylla™ MSI assay.

Main Methods:

• Retrospective review of 629 colorectal cancer cases.
• Comparison of results from Idylla™ MSI assay (293 cases) and IHC (336 cases).
• Confirmation of positive Idylla™ MSI results with subsequent IHC and other PCR-based methods.

Main Results:

• Idylla™ MSI detected dMMR in 18% (52 cases), while IHC detected it in 16% (55 cases).
• Results from both methods were comparable.
• One case initially positive by Idylla™ MSI was not confirmed by IHC but was validated by another PCR method, indicating no false positives in screening.

Conclusions:

• The Idylla™ MSI assay functions effectively as a screening method for dMMR in colorectal cancer.
• The proposed decision algorithm is practical and easy to implement.
• No false-positive screening results were observed, supporting the reliability of the Idylla™ MSI assay.