MMR-deficient (dMMR): Definition

by Jason Wasserman MD PhD FRCPC
March 23, 2026

MMR-deficient, often written as dMMR, means that one or more of the proteins responsible for repairing mistakes in a cell’s DNA are missing or not working properly. When these repair proteins are lost, errors in DNA can accumulate over time, contributing to the development of cancer. Finding dMMR in a tumour has important implications for treatment and may also have implications for you and your family.

What does MMR stand for?

MMR stands for mismatch repair — a system inside normal, healthy cells that acts like a spell-checker for DNA. Every time a cell divides and copies its DNA, small mistakes can occur. The mismatch repair proteins find and fix these mistakes before they can cause harm. The four main MMR proteins are MLH1, PMS2, MSH2, and MSH6. They work in pairs: MLH1 with PMS2, and MSH2 with MSH6.

When one or more of these proteins is lost, the repair system no longer works properly. This is called mismatch repair deficiency, or dMMR. The opposite — when all four proteins are present and working — is called MMR-proficient (pMMR).

How is dMMR detected?

Pathologists most commonly detect dMMR using a laboratory test called immunohistochemistry (IHC). This test uses special stains that make the four MMR proteins visible under the microscope. If one or more proteins cannot be seen in the tumour cells, that protein is reported as “lost” or “absent,” and the tumour is called MMR-deficient.

Because the proteins work in pairs, two proteins are often lost together. For example, a loss of MLH1 is usually accompanied by a loss of PMS2, and a loss of MSH2 usually accompanies a loss of MSH6. Your pathology report will typically specify which protein or proteins were lost.

dMMR can also be detected using a molecular test called microsatellite instability (MSI) testing, which directly examines DNA for the kinds of errors that accumulate when the MMR system is not working. Tumours that are dMMR by IHC are usually also reported as MSI-high (MSI-H) by molecular testing. These two terms — dMMR and MSI-H — are closely related and are often used interchangeably in cancer treatment.

What types of cancer are commonly tested for dMMR?

dMMR testing is now routinely performed on many cancer types. It is most commonly ordered for:

• Colorectal cancer (colon and rectal cancer) – dMMR is found in approximately 15% of colorectal cancers and is one of the most important biomarkers tested in this disease.
• Endometrial (uterine) cancer – dMMR is found in a significant proportion of endometrial cancers and has major implications for treatment planning.
• Gastric (stomach) cancer
• Small intestine cancer
• Other solid tumours – testing is increasingly being performed across many other cancer types, since the treatment implications of dMMR can apply regardless of the cancer’s origin.

Why does dMMR matter for treatment?

Finding dMMR in a tumour is one of the most clinically important results a pathology report can contain. It matters for treatment in two main ways.

• Immunotherapy response. Tumours that are dMMR tend to have a large number of DNA errors, which makes them more recognizable to the immune system. This means they are often good candidates for a type of treatment called immunotherapy — specifically, immune checkpoint inhibitors (such as pembrolizumab or nivolumab). These drugs help the immune system recognize and attack cancer cells. dMMR/MSI-H status is now an approved marker for immunotherapy in several cancer types, and in some cases, it is used to guide treatment regardless of where the cancer started.
• Chemotherapy response. In some cancers, particularly colorectal cancer, dMMR tumours may respond differently to certain chemotherapy drugs compared to MMR-proficient tumours. Your oncologist will take your dMMR status into account when planning your treatment.

Does dMMR mean I have Lynch syndrome?

Not necessarily — but it is an important possibility worth investigating. There are two main reasons a tumour can be dMMR:

• Somatic (acquired) loss – The MMR protein was lost only in the tumour cells due to changes that occurred during cancer development. This is not inherited and does not affect the rest of your cells. The most common acquired cause is a chemical change called MLH1 promoter methylation, which silences the MLH1 gene and leads to loss of both MLH1 and PMS2. This is the most common cause of dMMR overall, particularly in colorectal and endometrial cancers.
• Lynch syndrome – A hereditary condition in which a person is born with one faulty copy of an MMR gene. People with Lynch syndrome have a significantly increased lifetime risk of developing colorectal cancer, endometrial cancer, and several other cancers. Lynch syndrome is inherited.

Because dMMR can be caused by Lynch syndrome, most guidelines recommend that patients with dMMR tumours be referred to a genetic specialist for further evaluation. Additional tests — including blood or saliva-based genetic testing — can help determine whether the dMMR result is due to Lynch syndrome or an acquired change in the tumour.

If Lynch syndrome is confirmed, this information is also relevant for your biological relatives, who may wish to consider genetic counselling and screening.

What will my pathology report say if my tumour is dMMR?

Your report may use several different terms to describe this finding.

Common phrasings include:

• “MMR-deficient” or “dMMR”
• “Loss of [protein name] expression” — for example, “loss of MLH1 and PMS2 expression”
• “Absent staining for [protein name]”
• “Consistent with mismatch repair deficiency.”

If molecular MSI testing was also performed, the report may additionally state “MSI-high” or “MSI-H.”

Questions to ask your doctor

• My report says my tumour is dMMR — which proteins were lost?
• Does this result affect which treatments I am eligible for, including immunotherapy?
• Should I be tested for Lynch syndrome?
• Do my family members need to be informed or tested?
• Will my dMMR status be reassessed if I receive further treatment or surgery?