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Understanding Your Report · Reviewed by CION Oncologists · NABH Accredited
MMR & MSI-H Testing — What Your Report Actually Says
Somewhere on an endometrial cancer pathology report there is usually a line about mismatch repair — written as dMMR or pMMR, or as MSI-High or MSS. It looks like jargon and it worries people, partly because searching it leads straight to pages about inherited cancer syndromes. Here is the short version: this test is asking whether the tumour’s DNA proofreading system was working. The answer matters for two quite separate reasons — it affects which treatments are likely to work, and it acts as a first filter for Lynch syndrome. An abnormal result is common, and most of the time it is not inherited.
- It is done on tissue you already gave — no extra procedure — the biopsy or surgical specimen is used
- dMMR is common and usually not inherited — most abnormal results come from a change confined to the tumour
- It affects treatment choice — mismatch-repair-deficient tumours respond notably well to immunotherapy
- CION tests every tumour — as standard on every endometrial cancer, not only on request
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What the Test Is Asking
When a cell divides it copies its entire DNA, and it makes copying errors every time. A group of genes called the mismatch repair genes act as proofreaders, spotting those errors and fixing them before they are passed on.
This test asks a single question about your tumour: was that proofreading system working in these cells? There are two ways of asking it, and they are two routes to the same answer:
- MMR immunohistochemistry — the tumour is stained for the four repair proteins. If a protein is missing, the gene that makes it was not working. Reported as dMMR (deficient) or pMMR (proficient).
- MSI testing — instead of looking for the proteins, this looks for the fingerprint their absence leaves. Repetitive stretches of DNA called microsatellites accumulate errors when repair fails. Reported as MSI-High or MSS (stable).
The two tests usually agree. dMMR and MSI-High mean essentially the same thing; pMMR and MSS mean essentially the same thing. Which test your report shows depends on the laboratory, not on your cancer.
Nothing extra is taken from you for this. The test runs on the tissue removed at your endometrial biopsy or at surgery. There is no additional procedure and no blood test at this stage.
Did You Know? Mismatch repair deficiency is far more common in endometrial cancer than most people expect — it is one of the defining features of a whole molecular subgroup of this disease, not a rare curiosity. That is exactly why an abnormal result should not be read as a genetic diagnosis. The great majority of dMMR endometrial cancers are caused by a chemical modification that switches off one repair gene in the tumour tissue alone. It cannot be inherited, cannot be passed to children, and disappears with the tumour. Sources: NCCN Clinical Practice Guidelines in Oncology — Uterine Neoplasms; ESMO Clinical Practice Guidelines for endometrial carcinoma; The Cancer Genome Atlas molecular classification of endometrial carcinoma.
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Reading Your Result
| Result | Also written as | What it means |
|---|---|---|
| pMMR | MSS, microsatellite stable, mismatch repair proficient, “retained expression” | The proofreading system was working. Lynch syndrome is unlikely and the genetics pathway usually stops here. Treatment is guided by stage, grade and other molecular features rather than by this result. |
| dMMR | MSI-High, MSI-H, mismatch repair deficient, “loss of expression” | The proofreading system failed in this tumour. Common in endometrial cancer. It opens two questions: whether immunotherapy is likely to help, and why the system failed — a tumour-only change, or an inherited one. |
| Hypermethylation present | MLH1 promoter methylation, “epigenetic silencing” | A follow-on test run when dMMR is found. It identifies the tumour-only cause — a chemical switch, not an inherited fault. This explains most dMMR results, and where it is found, Lynch syndrome is effectively excluded. |
| dMMR, no methylation | “Unexplained” or “unmethylated” dMMR | The tumour-only explanation does not apply, so an inherited cause is possible. This is the result that leads to genetic counselling and, if you choose, a blood test. Still not a Lynch diagnosis — only germline testing gives that. |
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A Line on a Report Should Not Be Left Unexplained
If nobody has talked you through what dMMR or MSI-H means for your treatment, that is worth one appointment.
What the Result Changes
Three separate things follow from this line on your report, and it helps to keep them apart because they run on different timescales.
1. Which treatments are likely to work
Tumours with failed mismatch repair accumulate large numbers of DNA errors, which makes them look conspicuously abnormal to the immune system. That is why they respond notably well to immunotherapy — a genuinely important option in advanced or recurrent disease. See immunotherapy for MMR-deficient endometrial cancer.
2. Where the tumour sits molecularly
Endometrial cancers are now grouped into molecular categories that carry different outlooks, and mismatch repair status is one of the defining markers. It feeds into how the tumour board weighs radiotherapy and drug treatment alongside stage and grade. See molecular classification.
3. Whether to look for an inherited cause
This is the slowest-moving consequence and the one with implications beyond you. A dMMR result that is not explained by the tumour-only mechanism leads to counselling about testing for Lynch syndrome. Nothing about your relatives changes until that blood test is done and reported.
What it does not change
For early-stage disease, this result rarely alters whether you have surgery or what kind. Stage and grade remain the main drivers of the initial plan. Do not read a dMMR result as meaning your cancer is more serious — it does not mean that.
Told Your Tumour Is dMMR and Not Sure What Follows?
Bring the report. We will explain what it means for treatment, and whether a genetics conversation is warranted. The opinion is free.
The Confusions Worth Clearing Up
- dMMR is not a diagnosis of Lynch syndrome. It is a finding in the tumour that prompts a further question. Most dMMR endometrial cancers are not inherited.
- MSI-High is not “more aggressive”. It describes a DNA repair pattern, not a grade or a stage. If anything, it opens up an effective treatment option.
- The test was not done on your blood. Everything at this stage is on tumour tissue. Only germline testing looks at your inherited DNA, and it is separate, optional and preceded by counselling.
- pMMR does not exclude a hereditary cause absolutely. It makes Lynch unlikely, but a strong family history is still worth raising — see family history and endometrial cancer risk.
- Your relatives are not affected by this result on its own. Nothing changes for them unless and until an inherited variant is confirmed by a blood test.
Why CION Tests Every Endometrial Tumour
Testing only the women with an obvious family history misses a meaningful share of inherited cases. Universal testing is now the guideline standard, and it is what we do.
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Common questions
MMR & MSI-H Testing — Frequently Asked Questions
Does dMMR mean my cancer is more serious?
No. Mismatch repair status describes how the tumour cells handle DNA copying errors — it is not a measure of grade, stage or aggressiveness, which are what actually drive your outlook and your treatment plan. If anything, a dMMR result is useful news, because these tumours respond particularly well to immunotherapy if that becomes relevant. The molecular group a dMMR tumour usually falls into carries an intermediate outlook, generally better than the group defined by abnormal p53. Your stage and grade remain the numbers to ask about.
Do I need a blood test now that my tumour is dMMR?
Not necessarily, and not immediately. The next step is usually a further test on the same tumour tissue, checking for the chemical switch that silences a repair gene in the tumour alone. That switch explains most dMMR endometrial cancers, and where it is found, Lynch syndrome is effectively excluded and no blood test is needed. Only if that follow-on test does not explain the result would germline testing be discussed — and that discussion happens in genetic counselling first, so you can decide with a clear picture of what a result would mean for you and your relatives.
Which test is better, MMR immunohistochemistry or MSI?
Neither is straightforwardly better; they answer the same question from different angles and agree in the large majority of cases. Immunohistochemistry stains for the four repair proteins and has the practical advantage of showing which specific protein is missing, which helps direct any subsequent genetic testing. MSI testing looks at the DNA instability pattern that repair failure produces. Some laboratories run one, some the other, and some both when a result is unclear or the clinical picture does not fit. Which appears on your report reflects your laboratory rather than anything about your cancer.
How long do the results take?
The mismatch repair result is usually available within a week or two of the pathology report, often alongside it, because it runs on tissue the laboratory already holds. The follow-on methylation test, if needed, typically adds another week or two. Germline genetic testing is the slow step — several weeks at minimum, sometimes longer, because it involves counselling first, then sequencing, then interpretation. Importantly, none of this normally delays your treatment. Surgery and the initial plan proceed on stage and grade, and the genetics runs alongside.
Will my treatment change if I am dMMR?
For early-stage disease treated with surgery, usually not — the operation and whether radiotherapy is advised are decided mainly by stage, grade and depth of invasion. Where the result becomes genuinely important is in advanced, recurrent or metastatic disease, where mismatch repair deficiency predicts a strong response to immunotherapy and can change the treatment approach substantially. It also feeds into molecular classification, which the tumour board uses when weighing whether additional treatment after surgery is justified in borderline cases.
Medical disclaimer: This page explains terminology found on pathology reports and is reviewed by a CION oncologist. It is general health information, not an interpretation of your individual result, and it cannot replace a discussion with the team treating you. Take your actual report to your oncologist.