MSI-high tumors (MSI-H) are cancers with high microsatellite instability—basically, their DNA repair system is broken, so mutations pile up quickly.
What “MSI-high” means
- MSI = Microsatellite Instability
- Microsatellites are short, repeated DNA sequences
- In MSI-H tumors, the mismatch repair (MMR) system doesn’t work properly
- Result: lots of DNA errors → lots of mutations
This usually happens because key MMR genes (like MLH1, MSH2, MSH6, PMS2) are missing or inactive.
Why MSI-H matters (a lot)
- Have many mutations
- Make abnormal proteins (neoantigens)
- Are more visible to the immune system
That’s why they often respond very well to immunotherapy.
Cancers commonly MSI-high
MSI-H is most often seen in:
- Colorectal cancer
- Endometrial (uterine) cancer
- Gastric (stomach) cancer
- Ovarian, pancreatic, biliary, small bowel (less common)
Treatment implications
Big deal in oncology:
- Immune checkpoint inhibitors (like pembrolizumab or nivolumab) work especially well
- In some cancers, MSI-H status matters more than where the cancer started
- FDA approvals exist for tumor-agnostic treatment based on MSI-H status
In contrast, some standard chemotherapies work less well in certain MSI-H cancers.
How MSI-H is tested
- PCR testing for microsatellites
- Immunohistochemistry (IHC) for MMR proteins
- Next-generation sequencing (NGS) panels
Genetic angle (important)
MSI-H can be:
- Sporadic (most cases)
- Or due to Lynch syndrome (inherited)
That distinction matters for:
- Family cancer risk
- Screening recommendations