{"entity":{"id":"paper-cohen-msi-dmmr-misdiagnosis-colorectal-jama-oncol-2019","kind":"paper","name":"Association of primary resistance to immune checkpoint inhibitors in metastatic colorectal cancer with misdiagnosis of microsatellite instability or mismatch repair deficiency status","aka":[],"tldr":"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.","summary":"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.\n\nPrimary 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.","asOf":"2026-10-20","links":[{"label":"Cohen et al., JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2018.4942"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30452494/"}],"tags":["precision"],"related":[],"cancers":["msi-high-colorectal"],"sections":["diagnostics"],"technologies":["msi-mmr-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.4942","pmid":"30452494","authors":"Cohen R, Hain E, Buhard O, et al.","paperType":"observational","findings":["Positive predictive value of local MSI or dMMR results: 92.1 per cent in 38 treated patients and 90.3 per cent in 93 retrospective cases.","3 of 5 tumours with primary resistance to checkpoint inhibitors were not MSI or dMMR on central retesting.","A third assay (HT17) settled 2 of 4 cases where immunohistochemistry and PCR disagreed."],"whatItMeans":"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.","caveats":["Small numbers, as the authors say; larger studies were called for.","French laboratories in 1998 to 2016; testing practice has changed since."],"participants":131},"route":"/key-papers/paper-cohen-msi-dmmr-misdiagnosis-colorectal-jama-oncol-2019/","neighbours":{"cancer":[{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}]}}