Microsatellite Stability Biomarker (MSS)
What is the MSS biomarker?
Each of our cells contains DNA with genes that provide instructions for our cells on how to grow, carry out specific activities, divide, or die. The DNA in our cells also contains segments of short repetitive DNA sequences called microsatellites. This microsatellite DNA serves as a biomarker for how stable our DNA is.
The DNA is considered stable when the number of microsatellite repeats is the same in all the cells of the body, also referred to as microsatellite stable or MSS.
DNA mismatch repair (MMR) is a quality control and “spell checking” process that is responsible for making sure the DNA is copied without errors. When this is right, the number of microsatellite repeats is the same in all the cells. The MMR process relies on four main proteins: MLH1, MSH2, MSH6, and PMS2 that work together to repair mistakes in the DNA.
In some cancer patients, the MMR process works well. For these people, the cancer cells are proficient in mismatch repair (pMMR) and their tumor cells have the same number of repeats as in their healthy cells. This is also referred to as microsatellite stable or MSS.
What does the MSS biomarker mean?
When and how should I have microsatellite testing?
Because MSI-H can be hereditary and additional family members could be at risk, every patient diagnosed with colorectal cancer should be tested and know if they are MSS or MSI-H. If the tumor is positive for MSI-H, additional tests (immunohistochemistry (IHC) or genetic testing for inherited mutations) are required to determine if they have Lynch syndrome.
What do I do with this information?
Knowing your tumor biomarkers can help you and your doctor make decisions about personalized treatment with therapies tailored specifically to the characteristics of your tumor.
Patients diagnosed with an MSS tumor have a higher risk of recurrence. If you have MSS metastatic disease, request testing for additional biomarkers including KRAS/NRAS, BRAF, and HER2.
Patients diagnosed with Lynch Syndrome should talk with their family members about their diagnosis, encourage them to get tested for Lynch syndrome, and get screened often for colorectal cancer and other cancers even if they do not have any symptoms.
What treatment options are available?
Patients with MSS tumors are treated with fluorouracil-based chemotherapy such as 5FU, FOLFOX, FOLFIFRI or similar drugs. Currently, pembrolizumab has been approved for MSS tumors with a TMB (tumor mutational burden) greater than or equal to 10 which occurs in 3-10% of MSS. There are ongoing clinical trials for immunotherapy in combination with different drugs or for MSS patients.
What are the potential side effects of immunotherapy?
Because immunotherapy affects your immune system, you may experience inflammation in different parts of your body. In addition, some of the most common side effects of immunotherapy are dryness, itching, and rashes of the skin, being or feeling sick, fatigue due to anemia or a decrease in thyroid hormones, diarrhea or constipation, headaches, pain, and high temperature.
It's very unlikely that you will have all of these side effects, but you might experience some of them. If you are experiencing severe side effects, call your doctor immediately.
For more on side effects of other chemotherapy regimens, click here.
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