Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry
(IHC) or 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 in special circumstances or to screen for Lynch syndrome. However,
there are data in the literature which suggest that the two test types may not be
equal. For example, molecular epidemiology studies reported different rates of deficient
MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the
two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests,
especially in non-colorectal and non-endometrial cancers and in cases with unusual
dMMR phenotypes. There are also scattered clinical data showing 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 genetic MSI status are equal predictive markers of the
immunotherapies.
