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When colorectal cancers labelled mismatch-repair deficient did not respond to immunotherapy, three of five turned out on retesting not to be deficient at all; local results were wrong about one time in ten.
A post hoc analysis of a single-centre prospective cohort of 38 patients with metastatic colorectal cancer diagnosed as MSI or dMMR by local laboratories and treated in checkpoint inhibitor trials in 2015 and 2016, with a retrospective cohort of 93 such cases from six French hospitals. Every tumour was retested by immunohistochemistry for the four mismatch-repair proteins and by PCR with pentaplex markers and the HSP110 T17 repeat.
Primary resistance occurred in 5 of the 38 patients (13 per cent), and 3 of those 5 tumours were microsatellite stable or mismatch-repair proficient on reassessment. The positive predictive value of the local result was 92.1 per cent (95 per cent confidence interval 78.5 to 98.0) in the treated cohort and 90.3 per cent (82.4 to 95.0) in the retrospective cohort, where 9 of 93 had been misdiagnosed. The authors recommended testing by both immunohistochemistry and PCR before checkpoint inhibitors.
Before starting immunotherapy on a mismatch-repair result, especially when the cancer does not respond, it is worth asking whether the result was confirmed by a second method.
Shares JAMA Oncology and the tag precision.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) and the tag precision.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) and the tag precision.
Shares MSI and mismatch-repair testing, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares MSI and mismatch-repair testing, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares MSI and mismatch-repair testing, Mismatch-repair deficient (MSI-high) colorectal cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares MSI and mismatch-repair testing, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Mismatch-repair deficient (MSI-high) colorectal cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
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