Microsatellite Instability (MSI) testing is a molecular diagnostic test used to identify genetic changes in certain types of cancers, particularly colorectal cancer and endometrial cancer. MSI testing assesses the stability of microsatellites, which are short, repeated sequences of DNA scattered throughout the genome. In normal cells, these microsatellites are stable, but in some cancer cells, they can become unstable due to defects in the DNA repair mechanisms. MSI testing looks at the length of certain DNA microsatellites from the tumor sample to see if they have gotten longer or shorter as a measure of instability.

The MSI status is typically categorized as MSI-High (MSI-H), MSI-Low (MSI-L), or Microsatellite Stable (MSS). MSI-High (MSI-H) tumors show a high level of microsatellite instability. MSI-Low (MSI-L) tumors show a low level of microsatellite instability whereas microsatellite Stable (MSS) tumors show no microsatellite instability.

MSI testing is used to screen for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch syndrome, a hereditary condition that increases the risk of colorectal cancer and other cancers. Individuals with Lynch syndrome have a genetic predisposition to develop certain cancers due to mutations in mismatch repair genes. MSI-high tumors, those with a high level of microsatellite instability, have been shown to respond well to immunotherapy drugs called immune checkpoint inhibitors. These drugs help the immune system recognize and attack cancer cells. MSI testing is used to identify patients who might benefit from immunotherapy treatments.

The results of MSI testing, in combination with other genetic and pathological information, help oncologists tailor the most effective treatment plan for cancer patients.