Mismatch repair deficiency testing for immune checkpoint inhibitor therapy in genitourinary malignancies.

Abstract

DNA mismatch repair (MMR) proteins maintain genomic stability, and their deficiency (dMMR) results in hypermutability and microsatellite instability. The U.S. Food and Drug Administration (FDA) approved the immune checkpoint inhibitor pembrolizumab for use in any dMMR cancer but did not provide guidance regarding dMMR detection. This review examines laboratory methods (immunohistochemistry, polymerase chain reaction, and next-generation sequencing) for dMMR detection, emphasizing their sensitivity, specificity, and limitations. Using the current literature, we outline considerations for when to test and which method to use when assessing MMR status in genitourinary cancers.