This article is about microsatellite stability. If you’re looking for microsatellite instability, click here.
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.
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.
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.
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
The microsatellite instability result may be reported as
If your test result is microsatellite instability (MSI, MSI-High, or dMMR), please visit microsatellite instability.
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.
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.
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.
A biomarker is a piece of information about your health. Biomarkers include your blood pressure, your blood type, and cholesterol or blood sugar levels measured in a blood test. The biomarkers of cancer are also known as tumor markers.