What Is Microsatellite Instability?

by Kathleen Hall, MBA Health Writer

Microsatellite instability (MSI) doesn’t have anything to do with satellites in the sky. The term actually describes a situation in which there are problems in your DNA that are not fixed, Ursula Matulonis, M.D., tells HealthCentral. Dr. Matulonis is chief of the division of gynecologic oncology at the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute.

MSI status can affect your treatment of some cancers, including endometrial cancer, and may mean you are at higher risk for other specific cancers. Read on to learn more about how MSI occurs and what it may mean for your endometrial cancer risk.

Scientist in lab collect dna sample in test tube with cotton swab

Meet Your DNA

DNA is a molecule in every cell’s nucleus (center) that contains your hereditary information. The DNA molecule has two interwoven strands (picture a twisted ladder) consisting of four bases — pairs of smaller, complementary molecules — that keep the strands together through a chemical link. The sequence of the base pairs “spells out” your genetic code.

What Happens When Cells Divide?

When cells divide, for example to replace old cells or repair damaged tissue, the two DNA strands unwind and separate, and each strand becomes a template for creating new DNA. Your body must quickly copy your DNA without making errors.

Sometimes, Mistakes Occur During Cell Division

“Among the four base pairs that everyone has in their DNA, there’s a stretch of them where one gets repeated multiple times,” explains Jessica Lee, M.D., assistant professor of obstetrics and gynecology at UT Southwestern Medical Center. Because this pair keeps getting replicated, it’s prone to small errors, which can lead to bigger consequences because different proteins are made based on this template, she says.

We Have a Built-in Repair Mechanism to Correct Mistakes

These small errors are normal, Dr. Lee says, and everyone has them. Fortunately, we have a repair mechanism, called mismatch repair (MMR), that proofreads the new copy of your DNA, identifying and fixing these replication mistakes.

Occasionally, Mistakes Persist

Some people don’t have as robust a repair mechanism, says Dr. Lee. “These patients have what we call microsatellite instability.” MSI can happen at the body level (germline), in which the mutations are in all the tissues in your body, or just within the tumor cells. About 25 to 30 percent of endometrial cancer patients have problems with MMR.

MSI May Indicate You Have Lynch Syndrome

Some people with MSI also have Lynch syndrome, an inherited syndrome caused by mutations in genes in charge of DNA mismatch repair. Lynch syndrome increases your risk for certain cancers, including colon cancer, endometrial cancer, and stomach cancer. About one in 42 endometrial cancer patients have Lynch syndrome.

scientist looking in microscope

Testing Cancer for Microsatellite Status

Cancer institutions now routinely test all endometrial cancer tumors for MMR, says Dr. Matulonis. This testing is also a screen to identify patients who may be a part of a Lynch syndrome family. For them, genetic testing may make sense. Furthermore, some patients who have advanced endometrial cancers and MSI tumors may qualify for an immunotherapy drug that boosts the immune system’s ability to fight cancer.

Doctor holding endoscope before gastroscopy

What if You Have Lynch Syndrome?

By identifying individuals and families with Lynch syndrome, oncologists can help prevent other Lynch-related cancers. For example, your doctor might recommend you undergo frequent colonoscopies to screen for colon cancer, or regular biopsies to check for endometrial cancer. You may have preventive surgery to remove your uterus or ovaries once you’re done having children. “There are different ways we can monitor and do interventions to prevent people [with Lynch syndrome] from getting cancer,” says Dr. Lee.

Micrograph of endometrial adenocarcinoma

Lynch Syndrome and Endometrial Cancer

Although Lynch syndrome is usually associated with colon cancer, Dr. Lee says about 50 percent of all women with Lynch syndrome actually present with endometrial cancer first. She encourages women to be aware of any abnormal vaginal bleeding, which is the hallmark sign of endometrial cancer. If you have bleeding during menopause, or unusually heavy or frequent periods, definitely get it checked out, she says.

Grandparents and grandchildren

Final Note: Know Your Family History

“Be knowledgeable about the different genetic syndromes,” says Dr. Lee. “If you have a strong family history — if multiple family members have colon cancer, endometrial cancer, or stomach cancer — talk to your doctor. You, or your family members, may be candidates for genetic testing.” By identifying people with Lynch syndrome before someone is diagnosed with cancer, we can affect overall survival, she says.

Kathleen Hall, MBA
Meet Our Writer
Kathleen Hall, MBA

Kathleen Hall is a health writer who writes articles for consumer and health professionals as well as health care marketing material for corporate clients. Kathleen has a BS in psychology from the University of Maryland, an MBA from Virginia Commonwealth University and is a member of the Association of Health Care Journalists. She divides her time between Richmond, Virginia, and Bar Harbor, Maine. Kathleen is also a professional artist and runner.