biomarkersBiomarker

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

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.

Part ofMismatch repair proteins (MLH1, MSH2, MSH6, PMS2)· MLH1, MSH2, MSH6, PMS2Other readoutsMSI-high All readouts

Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

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.

IHC score 4 approval thresholds

What it means for a patient

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.

Scoring rule

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

Thresholds used in approvals

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

Drugs whose label names it

Pembrolizumab Dostarlimab Nivolumab

Companion diagnostics (FDA list)

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	Nivolumab Ipilimumab	P250004 (08/15/2025)

Tests that measure it

VENTANA MMR RxDx Panel

Trials that name this readout

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.