Evaluating mismatch repair deficiency for solid tumor immunotherapy eligibility: immunohistochemistry versus microsatellite molecular testing

While many landmark solid tumor immunotherapy studies show clinical benefits for solid tumors with high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR), the methodologies focus only on confirmatory polymerase chain reaction (PCR) testing for MSI-H. Because some tumors are either dMMR or MSI-H but not the other, clinicians must choose between two testing methods for a broad patient population. We investigated the level of correlation between MMR protein immunohistochemistry (IHC) and microsatellite PCR testing results in 62 cancer patients. Thirty-five of the 62 cases (56.5%) were MSI-H by PCR, whereas 35 (56.5%) were dMMR by IHC. MMR IHC results correlated well with MSI PCR in 32 co-positive cases (91.4%) and 24 co-negative cases (88.9%). Six discrepant cases (9.7%) were identified, among which three were MSI-H and MMR intact, and three were dMMR and microsatellite stable. The results of this study highlight the implications of dMMR/MSI testing strategies on precision oncology. Co-testing with both MMR IHC and MSI PCR may be an effective screening strategy for evaluating immunotherapy eligibility status for solid tumors. •Many landmark immunotherapy clinical trials refer to both high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR).•Some tumors are either dMMR or MSI-H but not the other.•Testing of tumors with only immunohistochemistry (IHC) or polymerase chain reaction (PCR) will falsely exclude some patients from immunotherapy.•Co-testing with both MMR IHC and MSI PCR is an effective screening strategy for evaluating the eligibility status for immunotherapy.