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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.
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.
In plain words · The four mismatch repair proteins proofread newly copied DNA; when a tumour loses one of them its DNA fills with small errors, and that state (dMMR or MSI-high) is what lets immunotherapy work across many cancers.
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.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
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.
“Deficient mismatch repair (dMMR) proteins: MLH1, PMS2, MSH2 and MSH6”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| MSI-H or dMMR, tumour-agnostic | Pembrolizumab | Metastatic cancer (cancer that has spread) | FDA | label |
| MSI-H or dMMR | Pembrolizumab | Mismatch-repair-deficient endometrial cancer | FDA | label |
| dMMR Dosing table wording; the indications section names dMMR recurrent or advanced endometrial cancer and dMMR solid tumours as determined by an FDA-approved test. | Dostarlimab | Mismatch-repair-deficient endometrial cancer | FDA | label |
| MSI-H or dMMR | Nivolumab | Colorectal cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| Ventana MMR RxDx Panel | Ventana Medical Systems (Roche) | Endometrial Carcinoma (EC) - Tissue | Dostarlimab | P200019 (04/22/2021) |
| Ventana MMR RxDx Panel | Ventana Medical Systems (Roche) | Solid Tumors | Dostarlimab | P210001 (08/17/2021) |
| Ventana MMR RxDx Panel | Ventana Medical Systems (Roche) | Solid Tumors | Pembrolizumab | P210001/S001 (03/21/2022) |
| Ventana MMR RxDx Panel | Ventana Medical Systems (Roche) | Endometrial Carcinoma (EC) - Tissue | Durvalumab | P210001/S013 (12/18/2024) |
| MMR IHC Panel pharmDx (Dako Omnis) | Agilent Technologies | Colorectal Cancer (CRC) - Tissue | NivolumabIpilimumab | P250004 (08/15/2025) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
For colon cancer that is mismatch-repair deficient (about 10-15% of colon cancers, more in older patients), a single short course of immunotherapy before surgery is now a reasonable standard and is far more effective than chemotherapy, which has little effect in this subtype. It requires testing every colon cancer for mismatch repair at diagnosis, before surgery. Whether some patients can safely skip surgery, as in dMMR rectal cancer, is the next question.
Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.
It tells the pathologist which pancreatic cancers to test for the one immunotherapy-responsive subgroup and how.
MSI testing has a very low yield in TNBC; TMB and PD-L1 are the immunotherapy biomarkers worth pursuing.
Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.
Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).
A Western benchmark for how rare MSI-high is in bile duct cancer; gallbladder cancer was not included, and the MSK gallbladder cohort's 2.5% by MSIsensor and the Indian 0.6% by panel bracket it.
It is the argument for sequencing every man with advanced prostate cancer rather than only the ones who look high risk: the phenotype is uncommon, it is invisible clinically, it opens the only durable immunotherapy route in this disease, and in one man in five it also identifies Lynch syndrome in the family.
Shares Mismatch repair deficiency and microsatellite instability in triple-negative breast cancer: a retrospective study of 440 patients, Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications, CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer, Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma.
Shares Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications, CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer, Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma, MSH2 loss in primary prostate cancer.
Shares CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer, Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations, Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma, MSH2 loss in primary prostate cancer.
Shares CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer, Tumour-agnostic (tissue-agnostic) approval, Gallbladder cancer, Metastatic cancer (cancer that has spread) and the tag biomarker.
Shares Tumour-agnostic (tissue-agnostic) approval, Gallbladder cancer, Metastatic cancer (cancer that has spread), Pancreatic ductal adenocarcinoma and the tag biomarker.
Shares Immunohistochemistry (IHC), Nivolumab, Gallbladder cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares Immunohistochemistry (IHC), Endometrial cancer, Triple-negative breast cancer (TNBC), Prostate cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Ipilimumab, Nivolumab and the tag biomarker.