Biomarker testing

MSI and TMB Testing: — What Your Biopsy Results Mean

MSI and TMB are two markers measured on your biopsy tissue. Both are used to predict whether your immune system is likely to recognise the tumour — and whether immunotherapy belongs in your treatment plan.

Medically reviewed by Dr. Bharati Devi Gorantla, Medical Oncologist, MBBS · MD · DM (Adyar, Chennai) · ECMO · MRCP SCE (UK) · Last reviewed September 2026

Two different measurements — MSI and TMB measure different things about your tumour's DNA. Both can influence whether immunotherapy is considered.
Tested from existing tissue — The test is usually done on the biopsy sample you have already had, without needing a new procedure.
Not ordered for every cancer — Which markers your oncologist orders depends on your cancer type — not every tumour needs both, and some need neither.
A high result needs context — What a high result means depends on your specific cancer and stage. Your oncologist interprets it alongside other information.

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MSI and TMB are markers measured on your biopsy tissue. MSI shows how well your tumour repairs its own DNA errors. TMB counts how many mutations are present overall. Both predict whether your immune system is likely to recognise the tumour — and therefore whether immunotherapy is likely to be useful for you.

What does MSI measure, and what does a high result mean?

MSI stands for microsatellite instability. Microsatellites are short, repeated sequences scattered through your DNA. When the tumour's DNA repair machinery is faulty, errors pile up in those sequences — and a test can detect that.

A result of MSI-High means the repair system is not working well. Tumours with faulty repair tend to carry many mutations, making them more recognisable to the immune system.

NCCN and ESMO guidance identifies MSI-High as a predictive marker for checkpoint inhibitor response across multiple tumour types. Whether it changes your treatment plan depends on your cancer type, stage, and what other markers show.

A result of MSS — microsatellite stable — means the repair system is intact. Immunotherapy via this marker is less likely to help in that case.

What does TMB measure, and what does a high result mean?

TMB stands for tumour mutational burden. It measures the total number of mutations found across a representative portion of the tumour's DNA.

Tumours with many mutations can produce abnormal proteins that the immune system may recognise as foreign. A higher TMB can — in some cancer types — indicate that immunotherapy is more likely to be active.

TMB is measured using next-generation sequencing on your biopsy tissue. The result is a number, and your oncologist uses a threshold to judge whether it is high. That threshold can vary between laboratories and guidelines.

TMB-High does not guarantee a response. Your oncologist will interpret the result alongside your MSI status, cancer type, and stage before drawing any conclusion.

How do MSI and TMB compare?

	MSI	TMB
What it measures	Whether the tumour's DNA repair system is working	How many mutations are present across the tumour's DNA
How it is tested	PCR or immunohistochemistry (IHC staining) on biopsy tissue	Next-generation sequencing (NGS) on biopsy tissue
Cancers where commonly ordered	Colorectal, endometrial, gastric, small intestine — some guidelines extend it to all solid tumours	Many solid tumours, especially when other markers are borderline
What a high result suggests	The repair system is faulty — the tumour may respond to immunotherapy	Many mutations present — the tumour may be more visible to the immune system
What a low result suggests	Repair is intact — immunotherapy via this marker less likely to help	Few mutations — less likely to respond via this pathway
Overlap between the two	MSI-High tumours often also have high TMB, because faulty repair leads to more mutations	TMB can be high even when MSI is stable — they do not always agree

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What to do when you get your MSI or TMB result

Ask your oncologist what the result means specifically for your cancer type — the same result can mean different things in different tumours.
Ask whether the result changes the treatment being recommended, and how.
Ask whether any other markers need to be tested before a final plan is made.
Keep a written copy of the report — you may need it if you seek a second opinion.
If genetic counselling is recommended alongside your MSI result, attend it — some MSI results point to an inherited cancer risk in the family.
Do not interpret the number in isolation. Your cancer type, stage, and other test results are what make it meaningful.

Terms you may see on your report

MSI-H: Microsatellite Instability-High. The tumour has accumulated many errors in its repeated DNA sequences, meaning the DNA repair system is not working correctly. This is the result associated with possible immunotherapy benefit.
MSS: Microsatellite Stable. The repeated DNA sequences show few or no errors. The repair system is intact. Immunotherapy via this marker is less likely to be useful.
MSI-L: Microsatellite Instability-Low. A borderline result. Most guidelines treat it similarly to MSS, but your oncologist will advise based on your specific cancer type.
dMMR: Deficient Mismatch Repair. This means the same thing as MSI-H but is arrived at by a different test — immunohistochemistry staining rather than PCR. Both describe the same underlying fault in the tumour's repair system.
pMMR: Proficient Mismatch Repair. This corresponds to MSS. The repair system is working. Your report may use dMMR or pMMR alongside — or instead of — MSI-H or MSS.
TMB-H: Tumour Mutational Burden-High. The tumour carries more mutations than a defined threshold, suggesting it may be more visible to the immune system. The exact threshold can vary between laboratories and the guidelines your oncologist follows.

Questions families ask about MSI and TMB

Does a high MSI result guarantee that immunotherapy will work?

No. MSI-High means the biology favours a response — it does not confirm that a response will happen. Response rates among MSI-High tumours vary across cancer types, and your oncologist will weigh the result alongside your stage, fitness, and other markers. What it does is shift the probability enough that immunotherapy is worth considering in your plan, where it might not have been otherwise.

Our report says dMMR. Is that the same as MSI-H?

Yes. dMMR and MSI-H describe the same underlying problem from two different angles. dMMR is detected by a staining test that looks directly at the repair proteins inside the tumour. MSI-H is detected by a molecular test that reads the DNA sequences themselves. The two results usually agree, and for treatment purposes they are interpreted identically. If your report gives one but not the other, ask your oncologist whether the second test adds anything in your situation.

Can an MSI result tell us whether cancer runs in our family?

Possibly, and it is worth asking. Some MSI-High results are caused by Lynch syndrome — an inherited fault in the DNA repair system that was present from birth and can be passed to children. Not all MSI-High tumours are caused by this; many are changes that happen only in the tumour itself. A separate blood-based genetic test can tell the two apart. If MSI-High has been confirmed and Lynch syndrome has not been discussed, ask your oncologist or request a genetic counselling referral.

Why does TMB matter if MSI already covers the same ground?

They overlap but are not identical. MSI-High tumours usually have high TMB, because faulty repair leads to more mutations. But some tumours have high TMB through a different mechanism while their MSI is stable — and in those cases TMB catches what MSI misses. The reverse can also occur. For cancer types where MSI is the established marker, TMB adds limited extra information. Your oncologist will advise whether testing both is warranted for your situation.

The biopsy sample is from two years ago. Is the result still valid?

For most purposes, yes — MSI and TMB reflect the biology the tumour had when the biopsy was taken, and these characteristics tend to be stable. However, if your cancer has progressed significantly or been heavily treated since that sample, your oncologist may want a more recent biopsy. Older blocks can also have practical limits: too little tissue remaining, or degraded quality. Ask whether the existing sample is adequate before assuming a new procedure is needed.

The test is expensive. Is it essential?

That depends on what decision it informs. If your oncologist is considering immunotherapy, MSI and TMB testing is how they establish whether you are likely to benefit — proceeding without it means accepting a treatment with real side effects and no evidence it is indicated for your tumour. If immunotherapy is not being considered for your cancer type regardless, the test may not change the plan at this stage. Ask your oncologist directly: what decision will this result inform, and what changes if we do not do it?

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Common questions

Frequently asked questions

What is MSI testing on a biopsy?

MSI testing looks at short repeated sequences in your tumour's DNA to see whether the repair system is working. When it is not — a result called MSI-High — the tumour carries many mutations and may be more recognisable to the immune system. The test is done on your biopsy tissue, usually from a sample you have already provided, and the result helps your oncologist decide whether immunotherapy belongs in your treatment plan.

What is TMB and why is it tested?

TMB — tumour mutational burden — counts how many mutations are present in the tumour's DNA. It is measured using next-generation sequencing on your biopsy tissue. A higher TMB can mean the tumour is more visible to the immune system, which may make immunotherapy more likely to be active. Your oncologist interprets it alongside your MSI result, cancer type, and stage — it is not a standalone decision.

Which cancers is MSI testing routinely ordered for?

MSI testing is routinely ordered for colorectal, endometrial, gastric, and small intestine cancers. NCCN and ESMO now recommend it across a broader range of solid tumours because MSI-High can indicate immunotherapy benefit regardless of where the cancer started. Whether it applies to your cancer type is a question your oncologist will answer based on your specific diagnosis and treatment options.

How long does MSI or TMB testing take?

MSI testing by immunohistochemistry typically returns within one to two weeks. TMB, which requires next-generation sequencing, can take two to three weeks or longer depending on the laboratory. If the sample must be sent to a specialist laboratory, allow extra time for transport. Ask your team when the sample was sent and when a result is expected so you are not waiting without a timeline.

What does it mean if both MSI and TMB are low?

It means these two markers do not favour immunotherapy via these pathways. This does not rule out all immunotherapy — other markers such as PD-L1 may still be relevant — and it does not mean you are out of options. It means a different treatment approach is more likely to fit your tumour biology. Ask your oncologist what the recommended alternative is and what it is expected to achieve for your situation.

Can MSI or TMB testing be repeated if the first result is unclear?

Yes. If the sample was too small, too old, or the result is borderline, your oncologist may request a repeat biopsy or ask a second laboratory to review the same sample. A borderline MSI-Low result is one situation where switching between test methods — from PCR to immunohistochemistry, or vice versa — can help clarify the picture. Ask your oncologist whether the current result is clear enough to act on before proceeding.

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