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MMR staining on the tumour as a route into Lynch testing | CION Cancer Clinics
An MMR stain checks whether four repair proteins are present in a tumour. If one or two are missing, the tumour cannot fix its copying mistakes, and an inherited condition called Lynch syndrome is one possible reason. Often it is not. This page explains what each pattern usually means, when a blood test follows, and what a normal stain does and does not rule out. At CION Cancer Clinics in Hyderabad, our oncologists review your family history with you and guide you to the right genetic counselling and testing.
On this page
- How can a stain on the tumour point to Lynch syndrome?
- What do the different staining patterns usually mean?
- What happens after a protein is found missing?
- The words on a pathology report, in plain language
- What an abnormal stain changes, and what a normal one does
- What this page cannot tell you
- Four things families assume about the MMR stain
- Common questions about MMR staining and Lynch testing
The short answer
How can a stain on the tumour point to Lynch syndrome?
The stain checks whether four repair proteins are present in the tumour. If one or two are missing, the tumour's repair system is broken, and an inherited condition called Lynch syndrome is one possible reason. A missing protein is a signal to look further. It is not a diagnosis.
What the test actually is
MMR IHC stands for mismatch repair immunohistochemistry. In plain words, the pathologist applies a stain to thin slices of the tumour that was already removed at biopsy or surgery. Each stain shows whether one repair protein is there. No new sample and no extra procedure is needed, because the tissue is already in the lab.
Why it is done on so many tumours
Lynch syndrome raises the risk of bowel, womb and several other cancers, and most people who carry it do not know. Family history alone misses many of them. Many guidelines now suggest the stain for every bowel and womb cancer, whatever the patient's age, because it is a cheap and simple way to find the families worth testing.
The same stain also tells your oncologist whether immunotherapy may help. That treatment question is covered on our targeted therapy pages.Reading the pattern
What do the different staining patterns usually mean?
The four proteins work in pairs, so they tend to go missing in pairs. Which pair is missing decides the next step.
MLH1 and PMS2 missing
This is the most common abnormal pattern, and most of the time it is not inherited. Often the MLH1 gene has been switched off inside the tumour by a process called methylation, which happens more with age. A further tumour test checks for this before any blood test.
MSH2 and MSH6 missing
This pattern points more strongly towards an inherited cause. It usually leads straight to counselling and a blood test.
The blood test looks at
- The MSH2 gene itself
- A neighbouring gene called EPCAM, which can switch MSH2 off
MSH6 or PMS2 missing alone
A single missing protein usually points to a fault in that exact gene. A blood test for that gene is normally the next step, even when the family history looks quiet.
All four present
The repair system looks intact, and Lynch syndrome becomes much less likely. It is not ruled out completely. A strong family history can still justify a blood test.
Not sure whether this applies to you?
Ask an oncologistAfter an abnormal stain
What happens after a protein is found missing?
The pathologist reports the pattern
The report names each protein as present or lost. Your oncologist reads it alongside your age, your cancer type and your family history.
An extra tumour test, if MLH1 is lost
The same tissue is tested for methylation, and in bowel cancer often for a change in a gene called BRAF. If either is found, the loss is usually acquired and a blood test may not be needed.
Counselling and a blood test
If an inherited cause is still possible, a genetic counsellor explains what testing means for you and your family, then arranges a blood test for the Lynch genes.
Family testing, if a fault is confirmed
Brothers, sisters and children can then be tested for that exact fault. Those who carry it can start bowel screening early. Those who do not can return to routine care.
On your report
The words on a pathology report, in plain language
- Mismatch repair (MMR)
- The cell's spell-checker. Four proteins, called MLH1, MSH2, MSH6 and PMS2, fix copying mistakes when a cell divides.
- Immunohistochemistry (IHC)
- A stain that shows whether a protein is present in a slice of tissue. It is read under a microscope by a pathologist.
- dMMR or MMR deficient
- At least one repair protein is missing. The tumour cannot fix its copying mistakes properly.
- pMMR or MMR proficient
- All four proteins are present. The repair system looks intact.
- MSI (microsatellite instability)
- A different lab test that looks at the DNA for the damage a broken repair system leaves behind. It answers a similar question to the stain.
- Lynch-like
- A tumour with a missing protein where no inherited fault is found. Often both copies were damaged inside the tumour itself.
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Side by side
What an abnormal stain changes, and what a normal one does
Being straight with you
What this page cannot tell you
It cannot tell you whether you have Lynch syndrome. A stain on the tumour only raises or lowers the chance. The answer comes from a blood test, read with a genetic counsellor. What your specific result means is a question for the counsellor who ordered the test.
It cannot read your pathology report for you
Staining is sometimes patchy or hard to call, and reports vary between labs. A pathologist may ask for a repeat stain or an MSI test before giving a firm answer. Your oncologist knows which of these applies to your tissue.
Who this does not apply to
Most people whose tumour is stained will have all four proteins present, and for them the stain is the end of the Lynch question. Others will have MLH1 loss explained by methylation and will not need a blood test either. A missing protein alone does not mean your children are at risk.
If your report says a protein is lost and nobody has mentioned a genetics referral, ask your oncologist whether one is needed.Commonly believed
Four things families assume about the MMR stain
Not on its own. The loss is often caused by a change that happened only inside the tumour, especially when MLH1 is missing in an older person. Only a blood test can confirm an inherited cause.
A normal stain makes Lynch syndrome much less likely. It does not rule out every inherited cause of cancer. A family with many young diagnoses should still see a counsellor.
Many guidelines now suggest staining every bowel and womb cancer, at any age. Relying on age or family history alone misses many families who carry Lynch syndrome.
The stain uses the tumour already removed at biopsy or surgery. Tissue blocks are usually stored, so the test can often be done long after the operation.
Questions we are asked
Common questions about MMR staining and Lynch testing
Is MMR IHC a genetic test?
Not exactly. It looks at proteins in the tumour, not at your inherited DNA. It is a screening step that picks out the tumours most likely to be linked to Lynch syndrome. A separate blood test is what checks your genes.
Which cancers are usually stained?
Bowel and womb cancers most often, because Lynch syndrome is most closely linked to them. The stain may also be used for some stomach, small bowel, urinary tract and ovarian cancers. Your pathologist and oncologist decide whether it is useful for your tumour.
Can the stain be done on an old tissue block?
Usually, yes. Hospitals keep tissue blocks after surgery, and the stain works on stored tissue. This helps when a relative who had cancer has died and the family wants to know whether Lynch syndrome was involved. Ask the hospital that did the surgery.
What does MLH1 promoter methylation mean?
It means the MLH1 gene has been switched off inside the tumour, without the gene itself being faulty. It is usually acquired, not inherited, and is more common with age. When it explains the missing protein, a blood test for Lynch syndrome is often not needed.
Is the stain the same as MSI testing?
They answer a similar question in different ways. The stain shows which protein is missing, which points to the gene to test. MSI testing looks for the damage a broken repair system leaves in the DNA. Some labs use one, some both.
If a protein is missing, will my treatment change?
It may. Tumours with a broken repair system often respond to immunotherapy, and the result can shape decisions about chemotherapy in some bowel cancers. Your oncologist will explain what it means for your plan.
Should my children be tested because my tumour lost a protein?
Not yet. The first step is to find out whether the loss is inherited, by testing you. Only if a fault is confirmed in your blood are adult relatives offered testing for that exact fault. A counsellor will guide the order.
Where do I start if my report says dMMR?
Take the report to your oncologist and ask whether a methylation test or a genetics referral is the next step. Call the CION helpline if you are unsure who to approach, and someone will point you to the right clinic.
Meet CION's oncologists. Bring your family history or genetic report to them.
Our medical oncologists see people with a strong family history of cancer, arrange genetic counselling and testing where it fits, and plan the checks that follow.
Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
Dr. Bharati Devi Gorantla
MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
Dr. Owais Mohammed
MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
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Sources
- GeneReviews (NCBI) — Lynch Syndrome
- National Cancer Institute — Genetics of Colorectal Cancer (PDQ) - Health Professional Version
- NICE — Molecular testing strategies for Lynch syndrome in people with colorectal cancer (DG27)
- MedlinePlus Genetics — Lynch syndrome
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.
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Your report says a repair protein is missing. What now?
Tell us what the pathology report says and who in the family has had cancer. We will explain whether a genetics referral makes sense and arrange it if it does. One helpline serves every CION centre.