Do You Need MSI Analysis for Your Endometrial Cancer?

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Endometrial cancer is the most common gynecological cancer in the United States, estimated to affect 61,880 women for the first time in 2019. And of those women, 20-30 percent will have tumors with microsatellite instability (MSI). It’s important to know if MSI is causing your cancer because it can help your care team determine which type of treatment is best, and whether you may benefit from enrolling in a clinical trial. Read on to learn more.


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What is MSI?

First of all, it’s important to understand what MSI actually is. Microsatellites are copies of DNA sequences. DNA Mismatch Repair (dMMR) is the system that makes sure all the copies are correct. When dMMR isn’t working, the mistakes that result lead to microsatellite instability, or MSI.


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How does MSI cause cancer?

When dMMR fails to do its job, damaged cells continue to grow, resulting in tumors. Depending on the amount of microsatellite instability in each tumor, the tumors will be classified as MSI-high or MSI-low. Different treatments work better for each type.


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How do you know if your tumor was caused by Lynch syndrome or MSI?

To check if you have Lynch syndrome, doctors can test the tumor tissue that has been removed during surgery by performing an MMR test (and sometimes a second test to confirm), according to Ardeshir Hakam, M.D., a pathologist at the Moffitt Cancer Center. An MSI analysis is more complicated. But if dMMR is not working, doctors may want to see if it’s due to a hereditary condition called Lynch syndrome or if it’s sporadic MSI. MSI testing is often done by a lab method called PCR.


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Why is it important to know if you have Lynch syndrome?

It’s important to know if you have Lynch syndrome for two main reasons, according to Dr. Hakam: First, doctors can be on the lookout for other tumors and hopefully prevent them from progressing. Second, they can test family members to make sure they are not at risk. Patients who have Lynch syndrome need genetic counseling and close follow-up. Some cancer centers, such as Moffitt, test anyone with endometrial cancer for Lynch syndrome; others only test patients over a certain age.


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Is there an easy test for MSI not associated with Lynch syndrome?

There isn’t an easy test for MSI currently in use; some researchers have called out the need for one, however.


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How does knowing MSI levels affect treatment options?

Although patients with MSI-H generally have less aggressive cancer, chemotherapy often doesn’t work as well. That means doctors will determine whether patients with this type of tumor should have surgery alone or surgery plus newer immunotherapy drugs that have shown promising results for MSI-H.


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What about clinical trials?

Once you know the MSI status of your tumors, your care team can help you decide if you should enroll in a clinical trial. The FDA has already approved one immunotherapy drug (pembrolizumab) for any type of cancer with MSI-H tumors.


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What other types of cancer are caused by MSI?

MSI-H tumors are most common in colon cancer. They are also common in endometrial cancer, and they can be associated with many other types including breast, prostate, bladder, and thyroid.