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

Authors

Angela N Bartley
Anne M Mills
Eric Konnick
Michael Overman
Christina B Ventura
Lesley Souter
Carol Colasacco
Zsofia K Stadler
Sarah Kerr
Brooke E Howitt
Heather Hampel
Sarah F Adams
Wenora Johnson
Cristina Magi-Galluzzi
Antonia R Sepulveda
Russell R Broaddus

Publication Date

10-1-2022

Journal

Archives of Pathology & Laboratory Medicine

DOI

10.5858/arpa.2021-0632-CP

PMID

35920830

Abstract

Context.—: The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status.

Objective.—: To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy.

Design.—: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope.

Results.—: Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract.

Conclusions.—: An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories.

Keywords

Female, Humans, Colorectal Neoplasms, DNA Mismatch Repair, Immune Checkpoint Inhibitors, Microsatellite Instability, Pathologists, Pathology, Molecular, Systematic Reviews as Topic

Published Open-Access

yes

Recommended Citation

Bartley, Angela N; Mills, Anne M; Konnick, Eric; et al., "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" (2022). Faculty, Staff and Student Publications. 4932.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4932