Inside the USCAP Journals

Abstract

Insertion and deletion mutations in mononucleotide repeats are a molecular signature of mismatch repair deficiency, which can be used as a biomarker of immunotherapy response of Lynch syndrome–associated endometrial cancers as well as those with sporadic microsatellite instability. Dong et al. compared their sequencing results to tumors identified by immunohistochemistry (IHC) expression patterns for loss of MLH1, MSH2, MSH6, and PMS2 and classified 259 endometrial cancers as mismatch repair deficient, proficient, or intermediate, with an overall concordance between the two methods. Sequencing through their algorithm provided 94% concordance with IHC, but the authors note that IHC will remain the most costeffective method for identifying mismatch repair deficiency in endometrial cancers until targeted next-generation sequencing is in wide use for clinical cancer care. At that point, with gene panels of appropriate size, obtaining actionable information including determination of mismatch repair deficiency would potentially lead to increased clinical benefit relative to sequencing cost.