This article is about microsatellite stability. If you’re looking for microsatellite instability, click here.
What is the microsatellite stability or microsatellite stable biomarker?
The microsatellite stability (or microsatellite stable) biomarker gives information about how your cells handle errors that happen during cell processes.
During organ and tissue growth, or healing of organ and tissue damage, your cells divide to make more cells. As each cell splits, the DNA divides and makes a copy of itself for the new cells. This is called DNA replication. Mistakes that occur in the copying process are called DNA mismatches. The microsatellite stability status tells whether your cells can fix these mistakes. This is called DNA mismatch repair (MMR).
DNA mismatch repair is controlled by several genes, including MLH1, MSH2, MSH3, MSH6, MLH2, MLH3, PMS1, PMS2, and EPCAM. Mutations in these genes can cause mismatch repair deficiency. Germline (inherited) mutations in these genes cause Lynch Syndrome, a hereditary colorectal cancer syndrome. There are other genetic processes that affect gene and protein expression (phenotype), such as DNA methylation, which can also cause mismatch repair deficiency. These types of changes are not usually inherited.
Microsatellites are small, repetitive segments of genomic DNA. Microsatellite stability testing looks at whether these DNA segments have many mutations or few mutations. Mismatch repair status can also be tested by looking at the expression level of mismatch repair genes and proteins.
Microsatellite stability status is both a prognostic and a predictive biomarker. It gives information about the usual course of disease (prognosis) and it predicts which treatments may be more or less effective against a particular colorectal cancer, such as conventional chemotherapy drugs or immune checkpoint blockade with immunotherapy drugs.
What is the difference between microsatellite stability and microsatellite instability?
Microsatellite stability and microsatellite instability are the two opposite results of the same biomarker test.
When microsatellite DNA segments are unchanged (not mutated) in your colorectal cancer, the tumor (tumour) cells are considered microsatellite stable (MSS). MSS colorectal cancers have normal levels of mismatch repair gene and protein expression. Microsatellite stable cancer cells are able correct DNA mismatch repair errors proficiently.
When the microsatellite DNA segments in your cancer cells show changes (mutations), this indicates that the tumor cells are deficient in the repair of mismatch errors. These colorectal cancers have microsatellite instability (also called MSI-High, MSI-H, or mismatch repair deficiency, dMMR). MSI tumors may have abnormal levels of mismatch repair gene and protein expression due to mutation or other genetic processes.
How is the microsatellite stability biomarker tested?
Microsatellite stability (and microsatellite instability) are measured in a biopsy sample of your colorectal cancer (CRC). There are several laboratory methods that can be used, including immunohistochemistry (IHC), polymerase chain reaction (PCR), and next-generation sequencing (NGS).
When tumor tissue is not available, microsatellite stability and instability can be measured in circulating tumor DNA (ctDNA). ctDNA is fragmented DNA released by your cancer cells into the blood. ctDNA can be isolated from a blood sample for testing. This is also known as liquid biopsy.
How are the results of microsatellite stability testing reported?
There are two possible results for this test, but there are several terms used interchangeably for each.
The microsatellite stable result may be reported as
- Microsatellite stable (MSS)
- Microsatellite stability (MSS)
- Proficient mismatch repair (pMMR)
The microsatellite instability result may be reported as
- Microsatellite instability (MSI)
- Microsatellite instability-high (MSI-High, MSI-H)
- Deficient mismatch repair (dMMR)
If your test result is microsatellite instability (MSI, MSI-High, or dMMR), please visit microsatellite instability.
What does my microsatellite stability result mean?
If you have the MSS biomarker, this means that your cells can correct the errors that occur in DNA (DNA mismatch repair). Your cancer cells have proficient mismatch repair.
- Microsatellite stable is the most common result for this biomarker test.
- MSS occurs in 85% of all colorectal cancers.
- Microsatellite stability is more common in earlier stages of colon cancer and rectal cancer (stage I and stage II).
- Patients with the MSS biomarker have a higher risk of colorectal cancer recurrence. This may be a factor in choosing your adjuvant treatment plan. Talk to your healthcare team about how you will be monitored for recurrence during follow-up care.
How does the microsatellite stability biomarker result impact my treatment options?
- Patients with microsatellite stability cancers are typically treated with fluorouracil-based chemotherapy (for example, 5-FU, FOLFOX, FOLFIRI), or with other conventional chemotherapy (capecitabine, CAPOX).
- Immunotherapy with immune checkpoint inhibitors, such as pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy), is not usually used in colorectal cancers with microsatellite stability.
- However, if your MSS colorectal cancer also has a high tumor mutational burden (TMB), immunotherapy can be effective.
- Tumor mutational burden is a measurement of how many genetic mutations are found in the genes of your tumor cells in a specific amount of DNA.
- Approximately 3% of MSS colorectal cancers may also have TMB-High. In some studies, the incidence of this MSS and TMB-High subset is much higher, and more research is ongoing.
- Immune checkpoint inhibitors use your own immune system to kill cancer cells by promoting stronger responses against cancer cells from white blood cells in your tumor (tumor-infiltrating lymphocytes).
- If your colorectal tumor cells show microsatellite stability, talk to your oncologist and healthcare team about TMB testing and whether your results indicate immunotherapy as a treatment option.
There are ongoing clinical trials of new drug combinations, including immune checkpoint inhibitors and other targeted therapies, to treat MSS colorectal cancer. To learn more about clinical trials and how you can benefit, click here and talk to your oncology team.
Who should have microsatellite stability biomarker testing? When should testing be performed?
All colorectal cancer (bowel cancer) patients should have testing for microsatellite stability and microsatellite instability at the time of their diagnosis. It does not matter what stage you are at diagnosis, whether you have stage I, stage II, stage III, or metastatic colorectal cancer, microsatellite stability status should always be tested. If you have not been tested, or are unsure if you have had testing, please talk to your healthcare team.
If your test result is microsatellite instability (MSI, MSI-High, or dMMR), you will need testing for Lynch Syndrome, a hereditary cancer syndrome caused by deficient DNA mismatch repair.