AJSP2501 - CME/CMLE - Current laboratory testing practices for mismatch repair deficiency and microsatellite instability testing-Current laboratory testing practices for mismatch repair deficiency and microsatellite instability testing

Current laboratory testing practices for mismatch repair deficiency and microsatellite instability testing

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The article explores the current practices and testing methodologies of laboratories for mismatch repair (MMR) and microsatellite instability (MSI) prior to the introduction of new guidelines by the College of American Pathologists (CAP) and the Association of Molecular Pathology. It highlights that U.S. laboratories and academic hospitals perform more frequent testing compared to international labs and non-hospital sites. Immunohistochemistry (IHC) is identified as the most common modality, followed by polymerase chain reaction (PCR) and next-generation sequencing (NGS).<br /><br />The study, based on a survey of 542 laboratories, reveals domestic labs favor IHC, while international labs combine methods like PCR with IHC. Academic centers are more proactive in testing, indicating variation driven by the complexity of the facility's service offerings. Laboratories handle indeterminate results either by peer review or retesting, showcasing practice variability. Subclonal loss, indicating partial MMR gene function loss, is approached by diverse methods, such as repeating tests or using orthogonal techniques, underlining the lack of standardized protocols.<br /><br />NGS is the least utilized, but its usage is expected to grow due to its ability to evaluate many markers simultaneously. There is inconsistency in using tumor mutational burden (TMB) as a surrogate for MSI, with the survey highlighting educational opportunities on utilizing TMB correctly. While most labs recognize the link between test results and immune checkpoint inhibitor therapy, there's uncertainty around discordant results between testing methods.<br /><br />Though retrospective, the study offers insights into real-world laboratory practices, pointing out areas needing educational improvements and standardization, particularly concerning TMB's use and the handling of indeterminate or subclonal loss results. This baseline understanding could aid in assessing the impact of upcoming guidelines on lab practices.

Keywords

mismatch repair

microsatellite instability

College of American Pathologists

Association of Molecular Pathology

immunohistochemistry

polymerase chain reaction

next-generation sequencing

tumor mutational burden

immune checkpoint inhibitor therapy

laboratory practices