Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy

Published online before print January 5, 2023. DOI: 10.1200/JCO.22. 02462

Praveen Vikas, Hans Messersmith, Carolyn Compton, Lynette Sholl, Russell R. Broaddus, Anjee Davis, Maria Estevez-Diz, Rohan Garje, Panagiotis A. Konstantinopoulos, Aliza Leiser,  Anne M. Mills, Barbara Norquist, Michael J. Overman,  Davendra Sohal, Richard C. Turkington, and Tyler Johnson.

Purpose

The College of American Pathologists (CAP) has developed a guideline on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.

Methods

 The CAP guideline was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations.

Results

The ASCO Endorsement Panel determined that the recommendations from the CAP guideline, published on August 3, 2022, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer.

Recommendations

Within the guideline, MMR immunohistochemistry (IHC), MSI polymerase chain reaction, and MSI next-generation sequencing are all recommended testing options for colorectal cancer, MMR-IHC and MSI-polymerase chain reaction for gastroesophageal and small bowel cancer, and only MMR-IHC for endometrial cancer. No recommendation in favor of any testing method over another could be made for any other cancer. Tumor mutational burden was not recommended as a surrogate for DNA MMR deficiency. If MMR deficiency consistent with Lynch syndrome is detected, it should be communicated to the treating physician.

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