Does it matter whether one uses MSI PCR testing versus IHC for MMR deficiency testing in order to determine eligibility for immunotherapy?  

Immunohistochemistry (IHC) assays detect dMMR, or deficiency in the mismatch repair proteins. Polymerase chain reaction, or PCR, detects microsatellite instability-high (MSI-high) status at the genomic level. Functionally, they mean the same thing - tumors that test positive for either assay should ...

In colorectal cancers, PCR is likely more sensitive (+2-5%) for detecting MSI but more costly with a longer turnaround time. PCR may miss PMS2 and MSH6 alterations that are difficult to detect and are not always MSI-high (but they are germ-line alterations). IHC is easy to incorporate into universal...

Both IHC and PCR are sensitive and specific with a high concordance rate between these two methods (92–97%) (Sepulveda et al., PMID 28165299; Histopathology 2020). Importantly, there is a small percentage of dMMR CRCs with intact expression of MMR proteins by IHC, yet have a dysfunctional MMR ...

The answer in my practice is no. MMR IHC is an excellent screening tool and a quicker surrogate marker for MSI and is reflexively testing immediately on new CRC biopsies. I always check both for all of my patients, but in most cases, I do not wait for MSI testing on NGS prior to starting immunothera...