4.4 Article

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

期刊

HUMAN PATHOLOGY
卷 115, 期 -, 页码 10-18

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W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2021.05.009

关键词

Precision genomics; Microsatellite instability (MSI); Mismatch repair defi-ciency (dMMR); Precision immuno-therapy; Checkpoint inhibition; Testing discrepancy; Colorectal cancer; Solid tumors

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This study investigated the correlation between MMR protein immunohistochemistry (IHC) and microsatellite PCR testing in solid tumor immunotherapy, finding that in most cases, there is a good correlation between the two methods. Co-testing with both MMR IHC and MSI PCR may be an effective screening strategy for evaluating immunotherapy eligibility status for solid tumors.
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. (C) 2021 Published by Elsevier Inc.

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