Microsatellite instability

Immunotherapy is a cancer treatment that boosts the body’s immune system with medication so that it is better able to identify and destroy cancer cells. One commonly used type of immunotherapy is a newer category of drugs known as immune checkpoint inhibitors.

Immune checkpoints are a normal function of the body’s immune system. T-cells, a type of immune checkpoint protein cell found on immune cells, sometimes bind with a protein found on cancer tumor cells. When these cell types meet, this may turn off the immune system response, keeping it from destroying the tumor cells. Immune checkpoint inhibitor treatment turns off this checkpoint so that the immune system may destroy the cancer cells.

Microsatellite instability may impact how certain cancers respond to immunotherapy. Here’s what patients and their families need to know about microsatellite instability.

What are microsatellites and microsatellite instability?

For patients diagnosed with certain types of cancer, the care team may discuss the cancer’s microsatellite instability, also known as MSI. Microsatellites are short segments of DNA, the material that carries genetic code. A microsatellite generally consists of one to six base pairs that repeat several times.

Some microsatellites are unstable. Microsatellite instability occurs when a change happens to the DNA patterns of the microsatellite found within a cancer tumor that are different from what was originally inherited. Due to having a high number of DNA mutations, some cancers have high MSI. This means that the cells aren’t able to correctly repair themselves, and tumor cells may grow rapidly.

MSI is important because it may assist doctors in deciding on a patient’s cancer treatment plan.

Microsatellite instability is most commonly found in colorectal, endometrial and gastric cancers.

MSI testing

For patients with cancers known to have microsatellite instability, MSI testing may be recommended. This may help predict which cancer patients will respond best to immunotherapy.

MSI testing is performed on samples from a patient’s tumor. It’s generally based on five microsatellite markers. This type of testing may determine whether a tumor has high MSI, low MSI or is stable.

High (MSI-H): Tumors have a high MSI if at least two of the five markers show instability. In patients with colorectal cancer, high MSI means the patient is likely to have Lynch syndrome, the most common cause of hereditary colon cancer.

Low (MSI-L): Tumors with low MSI mean only one of the five markers show instability.

Stable (MSI-S): Microsatellite stable means none of the markers show instability.

Cancers with a high MSI are more likely to respond well to immunotherapy checkpoint inhibitor drugs because the mutations make it easier for the treatment to identify the cancer cells. For patients who have not been diagnosed with cancer but have a high or low MSI, genetic counseling and testing may be used to determine their colorectal cancer risk. For those with a stable MSI, genetic testing is generally not needed, as they are unlikely to have Lynch syndrome. However, testing still may be used if the patient has a family history of colorectal cancer.

Patients should always speak to their doctor to better understand what their MSI results mean for their cancer treatment options.