{"entity":{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","aka":["dMMR","MMR-deficient","mismatch repair deficient","MMRd","loss of MLH1","loss of MSH2","loss of MSH6","loss of PMS2","MMR IHC","MMR protein loss"],"tldr":"dMMR means one of the four mismatch repair proteins is missing from the tumour cell nuclei on a stain. It is the tissue-level twin of MSI-high and opens checkpoint immunotherapy in endometrial, bowel and many other cancers.","summary":"Immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 is read as retained or lost nuclear staining in tumour cells against an internal positive control; loss of any protein is mismatch repair deficient. Paired losses (MLH1 with PMS2, MSH2 with MSH6) reflect the heterodimers. Labels for pembrolizumab (tumour-agnostic, colorectal, endometrial), dostarlimab (endometrial and tumour-agnostic), nivolumab and ipilimumab (colorectal) and durvalumab (endometrial with chemotherapy) use 'MSI-H or dMMR' and name FDA-authorised tests; the VENTANA MMR RxDx Panel and the Agilent MMR IHC Panel pharmDx are the listed companion diagnostics. The dostarlimab label advises testing the primary tumour before temozolomide in gliomas because chemotherapy can alter dMMR results.","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":"Jemperli prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=095eab9f-545a-4f12-bfb7-19477fb901a5"}],"tags":["biomarker","mmr"],"related":["msi-high","tmb-high"],"cancers":["endometrial","endometrial-mmr-deficient","colorectal","gastric-msi-high","metastatic-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","dostarlimab","nivolumab","ipilimumab","durvalumab","ventana-mmr-rxdx"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","mlh1-promoter-methylation","ihc","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"mmr","measurement":"ihc-score","scoringRule":{"text":"Loss of nuclear staining for one or more of MLH1, PMS2, MSH2 and MSH6 in tumour cells, with retained staining in internal control cells, is mismatch repair deficient.","quote":"Deficient mismatch repair (dMMR) proteins: MLH1, PMS2, MSH2 and MSH6","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":"for the treatment of adult and pediatric patients with 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":"endometrial-mmr-deficient","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","quote":"KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation","status":"current"},{"value":"dMMR","drugId":"dostarlimab","cancerId":"endometrial-mmr-deficient","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=095eab9f-545a-4f12-bfb7-19477fb901a5","quote":"Monotherapy Adults with dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors 500 mg a JEMPERLI every 3 weeks for 4 cycles followed by 1,000 mg a JEMPERLI every 6 weeks for all cycles thereafter.","status":"current","note":"Dosing table wording; the indications section names dMMR recurrent or advanced endometrial cancer and dMMR solid tumours as determined by an FDA-approved test."},{"value":"MSI-H or dMMR","drugId":"nivolumab","cancerId":"colorectal","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f570b9c4-6846-4de2-abfa-4d0a4ae4e394","quote":"OPDIVO, in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC)","status":"current"}],"tests":[],"assays":["mmr-ventana"],"companionDiagnostics":[{"device":"Ventana MMR RxDx Panel","maker":"Ventana Medical Systems (Roche)","drugs":["dostarlimab"],"indication":"Endometrial Carcinoma (EC) - Tissue","pma":"P200019 (04/22/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Ventana MMR RxDx Panel","maker":"Ventana Medical Systems (Roche)","drugs":["dostarlimab"],"indication":"Solid Tumors","pma":"P210001 (08/17/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Ventana MMR RxDx Panel","maker":"Ventana Medical Systems (Roche)","drugs":["pembrolizumab"],"indication":"Solid Tumors","pma":"P210001/S001 (03/21/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Ventana MMR RxDx Panel","maker":"Ventana Medical Systems (Roche)","drugs":["durvalumab"],"indication":"Endometrial Carcinoma (EC) - Tissue","pma":"P210001/S013 (12/18/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"MMR IHC Panel pharmDx (Dako Omnis)","maker":"Agilent Technologies","companyId":"agilent","drugs":["nivolumab","ipilimumab"],"indication":"Colorectal Cancer (CRC) - Tissue","pma":"P250004 (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"}],"forPatient":"If your report shows loss of MLH1, PMS2, MSH2 or MSH6, your cancer is mismatch repair deficient. That opens immunotherapy (pembrolizumab, dostarlimab, nivolumab with ipilimumab depending on the cancer) and, because dMMR can be inherited as Lynch syndrome, your team should offer a germline test and advice for relatives. Loss of MLH1 alone is often caused by methylation rather than inheritance; a follow-up test tells the two apart."},"route":"/biomarkers/dmmr-ihc/","neighbours":{"biomarker":[{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"},{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"},{"id":"tp53-del17p","kind":"biomarker","name":"TP53 mutation and del(17p)","route":"/biomarkers/tp53-del17p/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"gastric-msi-high","kind":"cancer","name":"Microsatellite-unstable (MSI-high) gastric cancer","route":"/cancers/gastric-msi-high/"},{"id":"endometrial-mmr-deficient","kind":"cancer","name":"Mismatch-repair-deficient endometrial cancer","route":"/cancers/endometrial-mmr-deficient/"}],"drug":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"ventana-mmr-rxdx","kind":"drug","name":"VENTANA MMR RxDx Panel","route":"/drugs/ventana-mmr-rxdx/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mlh1-promoter-methylation","kind":"term","name":"MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)","route":"/terms/mlh1-promoter-methylation/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"}]}}