Related Experiment Video
Updated: Aug 15, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of
Praveen Vikas1, Hans Messersmith2, Carolyn Compton3
1University of Iowa, Iowa City, IA.
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.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.
Insights
The American Society of Clinical Oncology (ASCO) endorses the College of American Pathologists (CAP) guideline for mismatch repair (MMR) and microsatellite instability (MSI) testing. This guideline aids in selecting patients for immune checkpoint inhibitor therapy.
Area of Science:
- Oncology
- Molecular Diagnostics
- Clinical Practice Guidelines
Background:
- Immune checkpoint inhibitor (ICI) therapy efficacy is linked to specific tumor biomarkers.
- Mismatch repair (MMR) deficiency and microsatellite instability (MSI) are key biomarkers for ICI therapy.
- Standardized testing guidelines are crucial for consistent patient selection.
Purpose of the Study:
- To evaluate and endorse the College of American Pathologists (CAP) guideline on MMR/MSI testing for ICI therapy.
- To ensure clinical practice aligns with the latest scientific evidence for cancer treatment.
Main Methods:
- The CAP guideline underwent rigorous methodological review.
- An ASCO Endorsement Panel assessed the guideline's content and recommendations.
- ASCO's established procedures for guideline endorsement were followed.
Main Results:
- The ASCO Endorsement Panel found the CAP guideline clear, thorough, and evidence-based.
- ASCO officially endorses the CAP guideline titled 'Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy'.
- Specific testing recommendations vary by cancer type (colorectal, gastroesophageal, small bowel, endometrial).
Conclusions:
- MMR immunohistochemistry (IHC), MSI polymerase chain reaction, and MSI next-generation sequencing are recommended for colorectal cancer.
- MMR-IHC and MSI-PCR are recommended for gastroesophageal and small bowel cancers.
- MMR-IHC is recommended for endometrial cancer; tumor mutational burden is not recommended as a surrogate for MMR deficiency.
