MSI-high (MSI-H) is a status given to patients with cancer that indicates the presence of microsatellite instability. Microsatellite instability (MSI) is a change or mutation that occurs in short, repeated sequences of DNA—called microsatellites—and typically affects tumor cells. Cancer cells with high numbers of microsatellites are more vulnerable to mistakes when the DNA is copied in the cell. The primary cause of MSI usually points to a defective gene that impairs the cell’s ability to correct these mistakes in the first place. Microsatellite instability can result in the development of various cancers and is most commonly associated with colon cancers. Other cancers caused by MSI include:

  • Colorectal cancer
  • Endometrial cancer
  • Gastric cancer
  • Ovarian cancer
  • Urinary tract cancer
  • Hepatobiliary tract cancer
  • Brain cancer
  • Skin cancers

Microsatellite instability testing compares DNA sequences between tumor cells and normal tissue. MSI-high is a designation used for patients with cancer in which instability occurs in >30% of the targeted microsatellites. MSI-low (MSI-L), on the other hand, characterizes patients with a microsatellite instability of <30%. Patients who do not demonstrate any instability are said to be microsatellite stable (MSS). MSI-high is most prominent in a form of colorectal cancer called hereditary nonpolyposis colorectal cancer (HNPCC), otherwise known as Lynch syndrome. In fact, MSI testing has become a prevalent predictor for patients who risk developing Lynch syndrome. Many patients with MSI-H tumors have been found to be extremely responsive to certain immunotherapies—high microsatellite instability attracts large numbers of immune cells to the tumor, that are usually blocked from doing their job. Therefore, MSI testing is valuable as a diagnostic tool, as well as for making important treatment decisions.