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IHC Markers Explained

MMR Proteins and MSI: — What Your Report Means

Your report lists four protein names — each marked as retained or lost. This is your mismatch repair result, and it carries two direct consequences: one for treatment, one for your family.

Medically reviewed by Dr. Mohammed Imaduddin, Surgical Oncologist, MBBS · MS (General Surgery) · M.Ch (Surgical Oncology) · Last reviewed September 2026

  • Four proteins, one result — MLH1, PMS2, MSH2, and MSH6 are tested together. All four retained means proficient MMR. Any one lost means deficient MMR.
  • Two direct consequences — A deficient result influences immunotherapy eligibility and may prompt an investigation for Lynch syndrome, an inherited cancer condition.
  • One input among many — Your oncologist combines this marker with your cancer type, stage, and other results. No treatment decision rests on this alone.
  • Family history may become relevant — If the pattern of loss suggests an inherited cause, your oncologist may refer you to a genetics service.
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Your biopsy report tests four mismatch repair proteins — MLH1, PMS2, MSH2, and MSH6. When all four are present, the result is proficient MMR, or MSI-low. When any is absent, the result is deficient MMR, or MSI-high. Two things follow from that finding: it can determine immunotherapy eligibility and may point to Lynch syndrome.

What do MMR, dMMR, pMMR, MSI-H and MSS mean?

MMR (Mismatch Repair)
The cell's proofreading system — finds and fixes DNA copying errors. Four proteins carry it out: MLH1, PMS2, MSH2, and MSH6.
dMMR (Deficient MMR)
One or more of the four proteins is absent from the staining. The repair system is not working in that tumour.
pMMR (Proficient MMR)
All four proteins are present. The repair system is intact.
MSI-H (Microsatellite Instability-High)
The molecular consequence of dMMR. Short repetitive DNA sequences have accumulated errors. For most treatment decisions, MSI-H and dMMR are treated as equivalent.
MSS / MSI-L (Microsatellite Stable or Low)
Equivalent to pMMR. The repair system is working and errors have not accumulated.
IHC (Immunohistochemistry)
The staining method used on the biopsy slide to detect whether each protein is present or absent.

How do I find the MMR result in my pathology report?

  • Find the section headed MMR IHC, mismatch repair proteins, or microsatellite instability
  • Check each protein — MLH1, PMS2, MSH2, MSH6 — is listed as retained or lost
  • Note the overall call: dMMR or pMMR, and MSI-H or MSS/MSI-L
  • If any protein is listed as lost, note which one — the pattern matters for the steps that follow
  • Bring the full pathology report to your next appointment, not just the summary page

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Why does loss of an MMR protein matter to my treatment?

Loss of any MMR protein means the tumour's DNA repair system is not working. Your oncologist will consider two consequences of that finding.

The first is immunotherapy eligibility. Tumours with dMMR or MSI-H may be considered for a class of treatment called checkpoint inhibitors, because these tumours tend to be more visible to the immune system. Whether this applies to you depends on your cancer type, stage, and fitness.

The second is Lynch syndrome, an inherited condition that raises the lifetime risk of certain cancers. A dMMR result is not a diagnosis of Lynch syndrome — it is a prompt to investigate. Your oncologist may arrange additional testing or a referral to a genetics service.

Did you know?

The four MMR proteins work in pairs: MLH1 with PMS2, and MSH2 with MSH6. When the lead protein in a pair is lost, its partner usually disappears too — not because the partner gene is damaged, but because neither protein survives without the other.

Pathologists use this pairing pattern to help identify which gene may be the underlying cause, which shapes whether Lynch syndrome investigation is needed.

Source: NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal and Endometrial

What does this result mean for my treatment and my family?

Is dMMR always a sign of Lynch syndrome?

No. Most dMMR results — particularly in colorectal and endometrial cancers — are caused by a sporadic event called MLH1 promoter methylation, which is not inherited. Lynch syndrome accounts for a minority of dMMR cases. Distinguishing between the two requires additional testing, which your oncologist will arrange if the protein loss pattern raises the question. A dMMR result is the starting point for that investigation, not the conclusion.

Does a pMMR result mean immunotherapy is not possible for me?

It means this particular pathway — checkpoint inhibitors guided by MSI-H or dMMR status — is less likely to apply. Other biomarkers such as PD-L1 expression or tumour mutational burden may still be relevant depending on your cancer type. Your oncologist reviews the full picture of your results, not this marker alone. Being pMMR does not rule out all options, but this marker is not pointing toward that class of treatment.

What should I expect at my next appointment?

Your oncologist will explain how this result fits into your treatment plan. If immunotherapy is being discussed, this marker is one factor in that decision. If the result was dMMR, an additional test — commonly MLH1 methylation analysis — or a referral to a genetics service may follow. Bring the full pathology report and a note of any cancers in close relatives, particularly bowel, endometrial, or ovarian, as your family history will shape that conversation.

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Common questions

Frequently asked questions

What are the four MMR proteins and what do they do?

MLH1, PMS2, MSH2, and MSH6 are proteins that find and fix errors in DNA when cells divide — a proofreading system. They work in two pairs: MLH1 with PMS2, and MSH2 with MSH6. When any one is absent, copying errors accumulate in the tumour's DNA, changing how it behaves and how it may respond to certain treatments.

What does loss of a protein actually mean?

It means that protein was not detected in the tumour cells on the stained biopsy slide — the tumour is not producing it, so the repair system is not working. That result is recorded as dMMR. Whether the absence is caused by a sporadic change or an inherited gene fault is a separate question, and further testing can distinguish between the two.

Is MSI-H the same as dMMR?

For most treatment decisions, yes — they describe the same underlying state using two different methods. MMR IHC stains the biopsy slide to detect proteins. MSI testing looks at short repetitive DNA sequences for accumulated errors. In most cases they agree. Your report may show one or both results, depending on which tests were run.

Does a dMMR result mean I will have immunotherapy?

Not automatically. A dMMR or MSI-H result means checkpoint inhibitors are worth considering for certain cancer types, but your specific cancer, its stage, your fitness, and your other results all determine eligibility. Your oncologist makes that assessment. If immunotherapy is not recommended in your case, it is reasonable to ask why — the answer will be specific to your tumour.

I have a family history of bowel or womb cancer. Does this result change anything?

It may. A dMMR result alongside a family history of bowel, endometrial, ovarian, or urinary tract cancer raises the possibility that Lynch syndrome is involved. Tell your oncologist in detail — which relatives, which cancers, at what ages. This will shape whether a genetics referral is needed and how quickly.

What should I ask my oncologist about this result?

Three questions cover the essentials. Is my result dMMR or pMMR, and what does that mean for the treatments being considered? Does this result mean Lynch syndrome needs to be investigated, and if so what are the next steps? Are there other biomarker results from the same biopsy I should understand alongside this one? Write the answers down — these conversations are hard to recall clearly.

Full index

Browse all 701 biopsy topics

Every page in this section, grouped by the part of the journey it belongs to. Pick a group to see what is in it.

What Is a Biopsy?

What Is a Biopsy? Everything You Need to Know →

Types of Biopsy Compared

Which Biopsy Will You Have? Techniques Compared →

Preparing for a Biopsy

What to Expect on the Day of Your Biopsy →

Recovery and Aftercare

After a Biopsy: Recovery, Aftercare and Warning Signs →

Biopsy by Body Part

Biopsy by Body Part: What to Expect at Each Site →

Understanding Your Report

How to Read a Biopsy Report: Terms Explained →

IHC and Molecular Markers

IHC and Molecular Markers on a Biopsy: What They Mean →

Grading and Scoring Systems

Cytology & Prostate Scoring Systems Explained →

How Accurate Is a Biopsy?

How Accurate Is a Biopsy? Errors and Second Opinions →

If Your Result Is Benign

Your Biopsy Is Benign: What It Means and What Comes Next →

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