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“We need to check your tumour for MMR or MSI.” Another test name can feel like one more thing to understand when you are already dealing with cancer. These tests help your team learn how the cancer behaves and which treatments may be useful. They can often be done on tissue from a biopsy or operation you have already had.
You do not need to learn all the laboratory terms. The useful question is: “What does this result change about my care?”
What do MMR and MSI mean?
Inside a cell, deoxyribonucleic acid (DNA) carries instructions that help the cell function. Before a cell divides, it copies those instructions. Think of copying a long document: even careful copying can leave a few mistakes.
Genes are sections of DNA that carry instructions for making proteins. Proteins do much of the work inside cells, including repairing DNA. A change in a repair gene can leave its protein missing or present but not working properly.
Mismatch repair (MMR) is one of the cell’s proofreading systems, carried out by a team of repair proteins. These proteins help correct certain mistakes made when DNA is copied. Some stretches of DNA contain short patterns repeated many times. These are called microsatellites, and they are a normal part of our DNA.
Repeated text is easy to miscopy. A stretch with five repeats might become four or six. If these errors are not repaired, changes in repeat length can build up. This pattern is called microsatellite instability (MSI).
A small copying change, made visible
Each box shows the same two DNA letters, C and A.
We can check the repair proteins or look for the effects of faulty repair. MMR protein testing checks whether any of the repair proteins are missing from the cancer cells. MSI testing checks the DNA for changes in repeat length that can build up when repair is not working properly.
These are two ways of investigating the same process: one looks at the repair machinery, and the other looks for a consequence of its failure. The results usually fit together, but they do not always agree. Your team chooses the test or tests that best answer the question for your cancer.
How is the testing done?
The pathologist, a doctor who examines tissue, first checks whether the stored sample contains enough suitable cancer tissue. A new biopsy is not automatically needed. The test chosen depends on the cancer type and the question your team needs answered.
One tissue sample, different questions
Suitable tumour tissue, often from an earlier biopsy or operation
Are the repair proteins present?
Immunohistochemistry (IHC) uses special stains to look for the four repair proteins.
no stain in this exampleOther cells:
stain present
Reports which repair proteins are detected or missing.
Have the DNA repeats changed?
Polymerase chain reaction (PCR) copies selected DNA regions so their repeat lengths can be examined.
Next-generation sequencing (NGS) examines many DNA regions. Some validated panels assess MSI alongside other gene changes; not every panel does.
Reports whether the DNA repeats are stable or show instability.
A clear result from an appropriate test may be enough. A more expensive panel is not always more useful. IHC is an accepted clinical test, not simply a preliminary test that must always be confirmed.
Testing is particularly relevant in colorectal cancer, which affects the colon or rectum, and endometrial cancer, which starts in the womb lining. In other cancers, its usefulness depends on the diagnosis, stage and treatment choices. Our explanation of molecular testing puts these methods in the wider picture.
What if the tests disagree?
The tests often agree, especially in colorectal cancer, but occasional differences need expert review. A protein may be present yet not work properly. DNA changes can be subtle, or the amount and quality of tissue may affect the result.
The laboratory may recheck the slides, repeat a stain, examine another tissue block or use a different method. An uncertain result is not a definite normal result. Neither the more expensive test nor the more encouraging result should automatically overrule the other.
Methods also perform differently in different cancers. For example, professional guidance favours MMR protein testing for endometrial cancer. Your team should explain whether another test would change a decision, rather than repeating tests without a clear purpose.
Understanding the words on your report
The laboratory may report the repair proteins, the DNA pattern, or both. These are the main terms you may see.
| Result | What it means |
|---|---|
| dMMR | Deficient mismatch repair. The findings indicate that the tumour’s repair system is not working properly. |
| pMMR | Proficient mismatch repair. The findings support a working repair system. On protein testing, this usually means all four proteins are retained. |
| MSI-high or MSI-H | The DNA test has found enough instability to meet its criteria for a high result. |
| MSS | Microsatellite stable. The DNA test has not found the pattern required for an unstable result. |
| MSI-low | Some instability was found, below the test’s MSI-high threshold. This is not the same as MSI-high. |
| Uncertain or inadequate | The laboratory cannot give a confident result. This is not a definite normal result; review or further testing may be needed. |
“High” does not mean advanced cancer. MSI describes a feature of the tumour, while stage describes how far the cancer has grown or spread. Likewise, “deficient” does not mean you have a dietary protein deficiency.
A report saying only “positive” or “negative” can be confusing. Ask which test was performed and whether the conclusion is dMMR, pMMR, MSI-high or MSS. Your oncologist will interpret it alongside the rest of your reports.
The four protein names, with an example report
The usual panel checks proteins called MLH1, PMS2, MSH2 and MSH6. You do not need to memorise their names. They work in pairs: MSH2 with MSH6 helps recognise copying errors; MLH1 with PMS2 helps organise their repair.
“Retained” means a protein was detected. “Loss” means it was not detected in the tumour cells, with suitable testing controls. Loss of even one protein can be important. Because the proteins work together, two may be lost together.
An example report: “MLH1 and PMS2 lost; MSH2 and MSH6 retained.” Two proteins were not detected and two were detected. With appropriate test controls, this supports dMMR. It does not, on its own, explain why the proteins are missing or whether the cause is inherited. Your team may recommend further tests to clarify this.
What can this change about treatment?
Some DNA errors change the proteins a cancer cell makes. Small fragments of these altered proteins may be displayed on the cell’s surface. These unfamiliar fragments, called neoantigens, can help immune cells recognise the cancer. A T cell is one type of immune cell that can attack it.
Recognition alone may not be enough. The immune system has control signals, often described as brakes, that prevent excessive attacks on healthy tissue. Cancer can use these signals to hold back an immune response. Certain immunotherapy medicines, called immune checkpoint inhibitors, block a brake signal.
Helping immune cells act on what they recognise
An immune brake is active
The T cell may recognise an unusual protein fragment. A separate brake signal can still hold back its response.
A medicine blocks the brake
The green Y represents a checkpoint inhibitor. Blocking the brake may help the T cell attack the cancer.
A dMMR or MSI-high result can therefore identify an important treatment opportunity. It is a biomarker, a measurable feature that helps guide care. It does not guarantee that treatment will work or that the cancer will be cured.
Some cancers shrink or stay controlled for a long time. Others do not respond, or start growing again later. Your cancer type, stage, earlier treatment and general health still matter.
Examples in different cancers
Advanced colorectal cancer: dMMR/MSI-high can make checkpoint immunotherapy an established treatment option. The choice of medicine or combination depends on the individual situation.
Colon cancer after surgery: the ATOMIC trial showed benefit from adding atezolizumab to chemotherapy for stage III dMMR colon cancer. In October 2026, the United States Food and Drug Administration approved this approach. This is a specific setting, not a recommendation for every early cancer. Local approval, availability and suitability need to be checked.
Selected rectal cancers: immunotherapy can sometimes allow people with locally advanced dMMR disease to avoid immediate surgery. This requires specialist assessment and close ongoing monitoring. A complete clinical response means no cancer is detected by the assessments used; it is not a guarantee of permanent cure.
Endometrial cancer: immunotherapy combined with chemotherapy can help in some advanced or recurrent cancers with either dMMR or pMMR. The result does not have the same implications in every cancer type.
Other advanced cancers: MSI-high/dMMR may support treatment selected partly by the biomarker, rather than only where the cancer began. Eligibility still depends on the exact treatment setting and available options.
If the result is pMMR or MSS
This does not mean there are no treatment options. In most MSS colorectal cancers, a single checkpoint immunotherapy medicine is generally not effective enough to be used routinely. But that rule cannot be applied to every cancer. Some immunotherapy treatments are used without requiring MSI-high status.
Other biomarkers answer different questions. Programmed death-ligand 1 (PD-L1) is a protein involved in immune signalling. Tumour mutational burden (TMB) estimates the number of DNA changes in a measured amount of tumour DNA. Neither result is interchangeable with MMR or MSI.
Do not stop chemotherapy or another prescribed treatment because of the result alone. It may support using immunotherapy alone, combining treatments, or choosing a different approach. Your oncologist will explain the reason for the recommendation.
Immunotherapy can also cause inflammation in healthy organs and needs monitoring. Tell your team about autoimmune illness, an organ transplant or medicines that suppress immunity. If you are receiving treatment, follow their reporting instructions and read about immunotherapy warning signs. Significant new symptoms need prompt advice rather than waiting for the next routine visit.
Does this mean my cancer is inherited?
Not necessarily. Repair problems can develop only within the tumour. Sometimes, however, the finding suggests an inherited condition called Lynch syndrome, which increases the risk of certain cancers. A tumour result alone cannot diagnose Lynch syndrome in you or your relatives.
Your team considers the protein pattern, your age, your cancer history and your family history. Further tumour tests may help explain the finding. For example, a process called methylation can switch off the MLH1 gene without an inherited gene change being the cause.
If appropriate, you may be offered genetic counselling and a separate blood or saliva test. This asks whether you were born with a gene change that could also matter to relatives. If an inherited risk is confirmed, the family can receive specific advice about testing and surveillance. It does not mean that everyone with the gene change will develop cancer.
Making sense of your result together
Bring the full report to your appointment, rather than just a photograph of one line. Ask your team to explain the result in ordinary language and whether it changes a decision being made now. A caregiver can join the conversation and help you remember the explanation, if you would find that useful.
The next step may be a treatment discussion, clarification of an uncertain result, or an inherited-risk assessment. Ask when outstanding results are expected and who will explain them. Do not delay necessary treatment independently while arranging further tests.
You do not need to become an expert in the abbreviations. Understanding what the result means for your own care is enough.
Questions you may have
Will I need another biopsy or a blood test?
Often the laboratory can use stored tissue from an earlier biopsy or operation. Another sample may be needed if there is too little suitable tissue. Inherited-risk testing usually uses blood or saliva and answers a different question. Some specialist blood tests assess tumour MSI, but they are not routine blood counts and may miss a finding when little tumour DNA is circulating.
How long does testing take, and what will it cost?
Ask your team for the reporting time and cost of the particular test they recommend. A four-protein panel, focused MSI test and broader sequencing panel have different purposes and charges. Check what is already available from your previous reports before arranging another test.
Can food or supplements correct dMMR?
A dMMR result is not caused by eating too little protein. No diet or supplement is an established way to reverse the tumour’s repair defect. Nutrition can support your wellbeing, but it should not replace the recommended cancer treatment. Discuss supplements with your team before taking them.
Sources and further reading
- College of American Pathologists: MMR and MSI testing guideline
- National Cancer Institute: biomarker testing
- National Cancer Institute: immune checkpoint inhibitors
- NHS Genomics Education: mismatch repair and microsatellite instability
- MedlinePlus Genetics: Lynch syndrome
- FDA: atezolizumab with chemotherapy for stage III dMMR colon cancer
- FDA: nivolumab with ipilimumab for advanced MSI-high/dMMR colorectal cancer
- FDA: pembrolizumab with chemotherapy for advanced endometrial cancer
- Cercek and colleagues: nonoperative management of mismatch repair deficient tumours
- ASCO: locally advanced rectal cancer guideline
Medically reviewed and approved by Dr (Prof) Vijay Agarwal
Professor and Lead Consultant – Medical Oncology
