Microsatellite Instability Biomarker (MSI-H)

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 makes sure the DNA is copied without errors and that the number of microsatellite repeats remains 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 is defective. These cancer cells are "deficient" in mismatch repair (dMMR). The tumor cells in these patients may end up with too many microsatellite DNA repeats compared with their healthy cells. The inconsistent number of repeats is a biomarker for high microsatellite instability (MSI-H) and most likely dMMR.

Because MSI-H can be hereditary and other family members could be at risk, every patient diagnosed with colorectal cancer should be tested for the MSI-H biomarker. If the tumor is positive for MSI-H, additional tests (immunohistochemistry (IHC) or genetic testing for an inherited mutation) are required to determine if the MSI-H is caused by Lynch syndrome. First-degree relatives of Lynch syndrome patients (even those without symptoms) should discuss genetic testing for the same mutation with their doctor.

Knowing the details of 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 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 symptoms.
• MSI-H and dMMR are prognostic biomarkers. Overall, patients with MSI-H tumors have a better prognosis than patients with MSS tumors.
• MSI-H and dMMR are also predictive biomarkers that predict a positive response to immunotherapy, but do not respond well to fluorouracil-based chemotherapy (such as 5FU, FOLFOX, or similar drugs).

mmunotherapy treatments work by enabling the patient’s own immune system to fight and kill the cancer cells. Approved treatments with immune checkpoint inhibitors (Pembrolizumab or Nivolumab or a combination of Nivolumab and Ipilimumab) for patients with MSI-H or dMMR stage IV tumors are available. The response to these treatments is often positive and some patients may be cured.

There are also ongoing clinical trials with immunotherapy drugs for patients with advanced MSI-H/dMMR colorectal tumors as first-line therapy, and for non-metastatic, early-stage patients diagnosed with MSI-H/dMMR.

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.