AUTHOR=Nádorvári Maja L. , Lotz Gábor , Kulka Janina , Kiss András , Tímár József 

TITLE=Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 30 - 2024

YEAR=2024

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2024.1611719

DOI=10.3389/pore.2024.1611719

ISSN=1532-2807

ABSTRACT=Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or the molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only at special circumstances and to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. At first, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Secondly, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests especially in non-colorectal, non-endometrial cancers and in case of the unusual dMMR phenotypes. Thirdly, there are scattered clinical data that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and the genetic MSI status are equal predictive markers of the immunotherapies, which deserve attention.