{"entity":{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","aka":["MSI-high","microsatellite instability-high","mismatch repair-deficient","mismatch repair deficient","MMR-deficient","MMR deficiency","MMRd","MMR immunohistochemistry","mismatch repair immunohistochemistry","MMR IHC","mismatch repair proteins","MLH1, MSH2, MSH6 and PMS2","MSI by PCR","microsatellite instability testing","MSI testing"],"tldr":"Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise. It is found in a fraction of colorectal and endometrial cancers and was the basis of the first tumour-agnostic approval, pembrolizumab in 2017.","summary":"Microsatellite instability (MSI-H), or mismatch repair deficiency (dMMR), is the mark of a broken DNA spell-checker: loss of MLH1, MSH2, MSH6 or PMS2, through Lynch syndrome or sporadic MLH1 methylation, creates thousands of mutations and makes the tumour recognisable to T cells and therefore responsive to immunotherapy. It is found in a meaningful fraction of Colorectal cancer and Endometrial cancer. Pembrolizumab in MSI-H disease was the first tumour-agnostic approval, in 2017, and Dostarlimab achieves complete responses in dMMR rectal cancer without surgery. The biomarker is central to the KEYNOTE-177, CheckMate 8HW, NICHE-2, ATOMIC, AZUR-1 and RUBY trials and to the pairing of neoadjuvant checkpoint inhibitor with surgery or no surgery in dMMR colorectal cancer.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Microsatellite_instability","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Microsatellite_instability"}],"tags":[],"related":[],"cancers":["colorectal","endometrial","prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","dostarlimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-le-mmr-deficiency-pd1-nejm-2015","paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009","paper-markowitz-tgfbr2-inactivation-msi-colon-science-1995","paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014","paper-guedes-msh2-loss-primary-prostate-ccr-2017"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: 10 to 15% of resected disease but only about 5% of first-line metastatic disease (153 of 3,063; Venderbosch 2014) and 3.5% in one advanced cohort (Koopman 2009), because unstable tumours metastasise less readily. The mechanism that makes them cancers is slippage in coding microsatellites: TGFBR2 was the first such target identified (Markowitz 1995), and ACVR2A, RNF43 and B2M follow. The mechanism that makes them treatable is mutation load, a mean of 1,782 somatic mutations against 73 in proficient tumours (Le 2015)."],"category":"Biomarkers"},"route":"/terms/msi/","neighbours":{"cancer":[{"id":"advanced-adrenocortical-carcinoma","kind":"cancer","name":"Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)","route":"/cancers/advanced-adrenocortical-carcinoma/"},{"id":"advanced-small-bowel-adenocarcinoma","kind":"cancer","name":"Advanced and metastatic small bowel adenocarcinoma","route":"/cancers/advanced-small-bowel-adenocarcinoma/"},{"id":"advanced-recurrent-endometrial-cancer","kind":"cancer","name":"Advanced or recurrent endometrial cancer","route":"/cancers/advanced-recurrent-endometrial-cancer/"},{"id":"appendiceal-adenocarcinoma","kind":"cancer","name":"Appendiceal adenocarcinoma (mucinous and non-mucinous, including signet ring 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distal)","route":"/cancers/extrahepatic-cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"localised-small-bowel-adenocarcinoma","kind":"cancer","name":"Localised small bowel adenocarcinoma (stage I to III, resected)","route":"/cancers/localised-small-bowel-adenocarcinoma/"},{"id":"lynch-associated-colorectal-cancer","kind":"cancer","name":"Lynch syndrome-associated colorectal cancer","route":"/cancers/lynch-associated-colorectal-cancer/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal 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