Treating Colorectal Cancer: What All MSI-H Patients Need to Know

If you’ve been diagnosed with colorectal cancer, your doctor may have mentioned the term “microsatellite instability (MSI).” This refers to changes in microsatellites—the short, repeated sequences of DNA—that can be related to cancer, such as colorectal cancer.  

After a colorectal cancer tumor is surgically removed, it is tested under a microscope to determine “MSI status,” meaning it will either be MSI-high, (MSI-H),  MSI-low (MSI-L), or MSS (stable). 

“Determining if the tumor is MSI-high or -low can help the oncologist figure out the correct treatment plan for that particular patient,” says Rujuta Saksena, MD, hematologist and oncologist in New Jersey. 

Understanding Microsatellite Instability Status

MSI testing shows doctors the level of gene changes (mutations) within the colorectal cancer cells. Here’s how they determine MSI status when looking at the cells in a microscope: 

• MSI-H: Shows mutations in 30 percent or more of the microsatellite markers
• MSI-L: Fewer than 30 percent of the microsatellite markers are unstable
• MSS: None of the microsatellite markers show instability or changes

MSI-H occurs when genes that regulate DNA, called mismatch repair (MMR) genes, don’t work properly. MMR genes are like genetic “spell checkers.” As cells divide, MMR genes correct errors, like your computer’s spell checker would if you misspelled a word. 

“MSI testing helps determine if that spell checker within our cells functioning is faulty or not,” says Dr. Saksena. If the MMR genes are faulty, they won’t catch the “spelling” mistakes. This then allows the abnormal cells to grow unchecked and ultimately create the tumor. 

How MSI-H Status Guides Colorectal Cancer Treatment 

“MSI-high tumors typically ... grow undetected because they evaded the immune surveillance, which means that they basically dodged our immune system,” says Dr. Saksena. “So a great way to treat MSI-high tumors is with immunotherapy, which is a type of medication that activates the immune system to try and boost the body's innate responses against the cancer cells.”

“The treatment of colon tumors that are MSI-high has improved dramatically over the past several years with the addition of immunotherapy as part of the treatment regimen,” says Dr. Saksena. Colorectal cancers used to be treated with chemotherapy alone, which wasn’t always effective. 

“Colorectal tumors that are MSI-high now can be treated with a combination of chemo and immunotherapy or sometimes with just immunotherapy alone, which can really improve the response rates and help our body detect the cancer cells in a much more efficient way.”