AJMP2504 - CME/CMLE - Revision of interpretation criteria to define microsatellite instability in mismatch repair deficient neoplasms with subtle electropherogram changes-Revision of interpretation criteria to define microsatellite instability in mismatch repair deficient neoplasms with subtle electropherogram changes

Revision of interpretation criteria to define microsatellite instability in mismatch repair deficient neoplasms with subtle electropherogram changes

Back to course

Pdf Summary

In this study, researchers aimed to enhance the analytical performance of a microsatellite instability (MSI) assay in detecting mismatch repair-deficient (dMMR) endometrial cancers (ECs) by revising the criteria used to define MSI. Traditionally, MSI is characterized by shifts in microsatellite repeat sequences due to errors during DNA replication, which are typically recognized and repaired by the mismatch repair (MMR) system. When these proteins are deficient, these errors go unrepaired, leading to MSI. Previously, a 1-base shift or more was used to define MSI, but such criteria could introduce false positives. This research proposed utilizing a 2-base shift or more of the highest peak or the 5% peak (the leftmost peak with a peak height of at least 5% of the highest peak) to minimize false-positive results.<br /><br />The revised criteria improved sensitivity and specificity in identifying MSI, especially in non-colorectal cancers like ECs, compared to traditional methods. The study detailed that by adopting the revised criteria, the assay achieved higher accuracy in diagnosing ECs — demonstrating an 83% sensitivity and 89% accuracy rate, while maintaining 100% specificity.<br /><br />The study encompassed analyzing the electropherogram patterns of five mononucleotide microsatellite loci through both capillary electrophoresis and next-generation sequencing (NGS). It concluded that the usage of the 5% peak not only refined the interpretation of subtle electropherogram changes but also circumvented the subjective interpretation previously needed for assessing "shoulder patterns." These advancements underscore the critical role of refining diagnostic criteria to better elucidate the MSI status in various cancers, providing a more reliable marker for possible therapeutic interventions, including immunotherapy.

Keywords

microsatellite instability

mismatch repair-deficient

endometrial cancers

analytical performance

revised criteria

false positives

sensitivity

specificity

electropherogram patterns

next-generation sequencing