{"entity":{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","aka":["MSI-H","MSI-high","MSI high","microsatellite instability-high","microsatellite unstable","MSI status","MSI-H/dMMR","MSS","microsatellite stable"],"tldr":"MSI-high means the tumour's DNA has unstable repeat sequences, the footprint of failed mismatch repair. It is measured by PCR or sequencing, gives the same answer as dMMR in most tumours, and unlocks the same immunotherapies.","summary":"Microsatellite instability is scored by PCR across a panel of mononucleotide repeats (MSI-H when a set fraction of markers is unstable, typically 2 of 5 Bethesda or Promega markers, or 30 percent or more of a larger panel) or by next-generation sequencing algorithms that count unstable loci across hundreds of sites; MSS is stable and MSI-L is intermediate and grouped with MSS. Labels write 'MSI-H or dMMR' and accept either route; FoundationOne CDx and Caris MI Cancer Seek carry MSI-H companion claims for pembrolizumab and dostarlimab, the Biocartis Idylla MSI test for nivolumab in colorectal cancer, and, in the other direction, the Promega OncoMate MSI and Caris assays report 'not MSI-H' to select pembrolizumab with lenvatinib in endometrial cancer.","asOf":"2026-09-23","links":[{"label":"KEYTRUDA prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287"},{"label":"OPDIVO prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f570b9c4-6846-4de2-abfa-4d0a4ae4e394"}],"tags":["biomarker","mmr"],"related":["dmmr-ihc","tmb-high"],"cancers":["colorectal","endometrial","endometrial-mmr-deficient","gastric-msi-high","metastatic-cancer","tnbc","pancreatic","msi-high-pdac","gallbladder","cholangiocarcinoma","prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","dostarlimab","lenvatinib","foundationone-cdx","caris-mi-cancer-seek"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","mss-pmmr","ngs","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ren-tnbc-mmr-msi-440-front-oncol-2021","paper-kurata-japanese-tnbc-msi-breast-cancer-2020","paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018","paper-luchini-msi-dmmr-pancreatic-systematic-review-gut-2021","paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020","paper-le-mmr-deficiency-pd1-nejm-2015","paper-le-mmr-deficiency-science-2017","paper-keynote-177-nejm-2020","paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","paper-moreira-lynch-syndrome-identification-jama-2012","paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025","paper-goeppert-cholangiocarcinoma-mmr-deficiency-bjc-2019","paper-giraldo-gallbladder-msk-impact-ccr-2022","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":["Triple-negative breast cancer: MSI-high in 0 of 195 by PCR (Ren 2021) and 2 of 228, 0.9% (Kurata 2020); the rare positive qualifies for tumour-agnostic pembrolizumab and is best caught on a comprehensive panel rather than by dedicated testing.","Pancreatic ductal adenocarcinoma: MSI-high or mismatch repair deficient in about 1 to 2% and 0.8% of 833 MSK patients, every one of whom had Lynch syndrome (Hu 2018; Luchini 2021). It is the threshold for tumour-agnostic pembrolizumab, whose pancreatic cohort in KEYNOTE-158 gave 4 responses among 22 patients (Marabelle 2020), and the only approved immunotherapy route in this disease. Test medullary and colloid tumours specifically.","Colorectal cancer: MSI-high or mismatch repair deficient in 10 to 15% of resected disease but only about 5% of first-line metastatic disease (153 of 3,063; Venderbosch 2014). The threshold is binary and is the entry criterion for every colorectal immunotherapy trial: first-line pembrolizumab gave progression-free survival of 16.5 against 8.2 months (hazard ratio 0.60) in KEYNOTE-177, nivolumab gave 23 responses in 74 previously treated patients (Overman 2017), and four weeks of neoadjuvant nivolumab plus ipilimumab produced pathological complete response in 68% of locally advanced dMMR colon cancers (NICHE-2). Every colorectal cancer should be tested, because the same result identifies Lynch syndrome (Moreira 2012).","Gallbladder cancer: MSI-high in 6 of 244 samples (2.5%) by MSIsensor in cBioPortal gbc_mskcc_2022, 0.6% (2 of 170 tested) in Indian patients (Suryavanshi 2025) and 1.3% (4 of 308) in Western cholangiocarcinoma by a three-marker panel (Goeppert 2019). The tumour-agnostic pembrolizumab indication applies; the first-line biliary immunotherapy approvals were unselected.","Prostate cancer: microsatellite instability-high or mismatch repair deficient in 32 of 1,033 men with an assessable tumour, 3.1%, of whom 7, 21.9%, carried a pathogenic germline Lynch syndrome variant, and 2 of 6 men with serial tumours acquired the phenotype during their disease course. Eleven men received a PD-1 or PD-L1 antibody and 6, 54.5%, had a PSA fall of more than half, with 5 of the 6 responders still on treatment at up to 89 weeks (Abida 2019).","The mechanism differs from bowel cancer: among 60 advanced prostate cancers, 7 were hypermutated and all had mismatch repair gene mutations with microsatellite instability, frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 promoter methylation, so an assay designed around the colorectal mechanism can miss it (Pritchard 2014)."],"target":"mmr","measurement":"msi-status","scoringRule":{"text":"MSI-H: instability at the required fraction of tested microsatellite loci (for example 2 or more of 5 mononucleotide markers by PCR, or the sequencing panel's validated cut-off across many loci); otherwise microsatellite stable.","quote":"Microsatellite instability – High (MSI-H)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"MSI-H or dMMR, tumour-agnostic","drugId":"pembrolizumab","cancerId":"metastatic-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","quote":"unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-authorized test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.","status":"current"},{"value":"MSI-H or dMMR","drugId":"pembrolizumab","cancerId":"colorectal","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","quote":"for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-authorized test.","status":"current"},{"value":"MSI-H or dMMR (single agent after chemotherapy)","drugId":"nivolumab","cancerId":"colorectal","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f570b9c4-6846-4de2-abfa-4d0a4ae4e394","quote":"OPDIVO, as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.","status":"current"},{"value":"Not MSI-H / pMMR (selects the lenvatinib combination)","drugId":"lenvatinib","cancerId":"endometrial","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","quote":"KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by an FDA-authorized test","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","caris-mi-cancer-seek","tempus-xt","trusight-oncology-500","stratangs","omniseq-insight","altera","oncoextra","bostongene-tumor-portrait"],"assays":["msi-pcr","foundationone-cdx-panel"],"companionDiagnostics":[{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["pembrolizumab"],"indication":"Solid Tumors - Tissue","pma":"P170019/S029 (02/18/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"MI Cancer Seek (MCS)","maker":"Caris Life Sciences","companyId":"caris","drugs":["pembrolizumab"],"indication":"Solid Tumors - Tissue","pma":"P240010 (11/05/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"MI Cancer Seek (MCS)","maker":"Caris Life Sciences","companyId":"caris","drugs":["dostarlimab"],"indication":"Solid Tumors - Tissue","pma":"P240010 (11/05/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Idylla CDx MSI Test","maker":"Biocartis","drugs":["nivolumab","ipilimumab"],"indication":"Colorectal Cancer (CRC) - Tissue","pma":"P250005 (08/15/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"OncoMate MSI Dx Analysis System","maker":"Promega","drugs":["pembrolizumab","lenvatinib"],"indication":"Endometrial Carcinoma (EC) - Tissue","pma":"P240026 (11/05/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"MSI-high on a PCR or sequencing report means the same for treatment as dMMR on a stain: checkpoint immunotherapy is on label across many cancers once other treatment has been tried, and first line in bowel cancer. A stable (MSS) result in endometrial cancer selects a different combination, pembrolizumab with lenvatinib. Either result should prompt a conversation about inherited risk."},"route":"/biomarkers/msi-high/","neighbours":{"biomarker":[{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","route":"/biomarkers/dmmr-ihc/"},{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"}],"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"gastric-msi-high","kind":"cancer","name":"Microsatellite-unstable (MSI-high) gastric cancer","route":"/cancers/gastric-msi-high/"},{"id":"msi-high-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"},{"id":"endometrial-mmr-deficient","kind":"cancer","name":"Mismatch-repair-deficient endometrial cancer","route":"/cancers/endometrial-mmr-deficient/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"caris-mi-cancer-seek","kind":"drug","name":"MI Cancer Seek","route":"/drugs/caris-mi-cancer-seek/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"paper":[{"id":"paper-cercek-dostarlimab-rectal-nejm-2022","kind":"paper","name":"Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency","route":"/key-papers/paper-cercek-dostarlimab-rectal-nejm-2022/"},{"id":"paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014","kind":"paper","name":"Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer","route":"/key-papers/paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014/"},{"id":"paper-luchini-msi-dmmr-pancreatic-systematic-review-gut-2021","kind":"paper","name":"Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications","route":"/key-papers/paper-luchini-msi-dmmr-pancreatic-systematic-review-gut-2021/"},{"id":"paper-giraldo-gallbladder-msk-impact-ccr-2022","kind":"paper","name":"Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention","route":"/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/"},{"id":"paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025","kind":"paper","name":"Genomic profiling of Indian gallbladder carcinoma: mutational insights in a high-incidence population","route":"/key-papers/paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025/"},{"id":"paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018","kind":"paper","name":"Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations","route":"/key-papers/paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018/"},{"id":"paper-moreira-lynch-syndrome-identification-jama-2012","kind":"paper","name":"Identification of Lynch syndrome among patients with colorectal cancer","route":"/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/"},{"id":"paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020","kind":"paper","name":"KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer","route":"/key-papers/paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020/"},{"id":"paper-keynote-177-nejm-2020","kind":"paper","name":"KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer","route":"/key-papers/paper-keynote-177-nejm-2020/"},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","route":"/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/"},{"id":"paper-le-mmr-deficiency-science-2017","kind":"paper","name":"Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval","route":"/key-papers/paper-le-mmr-deficiency-science-2017/"},{"id":"paper-kurata-japanese-tnbc-msi-breast-cancer-2020","kind":"paper","name":"Microsatellite instability in Japanese female patients with triple-negative breast cancer","route":"/key-papers/paper-kurata-japanese-tnbc-msi-breast-cancer-2020/"},{"id":"paper-ren-tnbc-mmr-msi-440-front-oncol-2021","kind":"paper","name":"Mismatch repair deficiency and microsatellite instability in triple-negative breast cancer: a retrospective study of 440 patients","route":"/key-papers/paper-ren-tnbc-mmr-msi-440-front-oncol-2021/"},{"id":"paper-goeppert-cholangiocarcinoma-mmr-deficiency-bjc-2019","kind":"paper","name":"Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma","route":"/key-papers/paper-goeppert-cholangiocarcinoma-mmr-deficiency-bjc-2019/"},{"id":"paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","kind":"paper","name":"Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies","route":"/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/"},{"id":"paper-guedes-msh2-loss-primary-prostate-ccr-2017","kind":"paper","name":"MSH2 loss in primary prostate cancer","route":"/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/"},{"id":"paper-niche-2-nejm-2024","kind":"paper","name":"NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients","route":"/key-papers/paper-niche-2-nejm-2024/"},{"id":"paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017","kind":"paper","name":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142)","route":"/key-papers/paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017/"},{"id":"paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","kind":"paper","name":"Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade","route":"/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"}]}}