Microsatellite Instability (MSI)
- Microsatellites are parcels of DNA code
- Microsatillite Instability in those parcels (MSI)
- Mismatch Repair (MMR) our body’s dna spell checker
- Deficient Mismatch repair (dMMR) means failure of the spell checker
Microsatellite Instability occurs when the strings of dna contained within the microsatillites, replicate incorrectly creating errors in our dna code.
MSI is described as follows
- MSI-high: (MSI-H) occurs if two or more microsatellite markers show instability
- MSI-low: (MSI-L) occurs if there is only one marker unstable
- MSI-Stable : (MSS) results when all the five microsatellite markers are stable
Reporting often describes MSI as follows
- MSI-h > 30%
- MSI-L <30%
- MSS – 0% instability
MMR the Spell Checker
- MMR – means all genes are functioning / expressing correctly
- dMMR – when one or more genes are not expressing and correctly
There are 4 primary MMR genes are MLH1, MSH2, MSH6, and PMS2
Think of these genes as our body’s spell checkers, their job is to express proteins that fix / repair DNA replication errors as they occur. This is a normal function within our body.
What is it spell checking?
- Errors occur often in our DNA replication process.
- Microsatellites are parcels that contain strings of our pre-made dna code – the code that makes us – us!
- This replication process is constant and errors are normal
- When all 4 MMR genes are expressing proteins (spell checkers), then this is described as MMS (Stable).
When one or more of theses genes fail to express their proteins (spell checkers) this means the MMR process is now deficient and is not correcting all DNA mistakes as they occur. This then leads to accumulation of dna replication errors within the microsatillites creating microsatillite instabliity.
Uncorrected errors lead to accumulations of defective cells that cluster and can form cancer mutations.
Immnuotherapy and MSi-High
The MSi-high status has so far proven to perform best with Checkpoint Inhibitor Immunotherapy treatments, so this is the primary testing objective.
Testing for MSi-high
There are 2 primary testing methods to determine this, both require a tissue sample (biopsy)
- IHC fast efficient and inexpensive
- Molecular profiling more expensive and slower
- Blood Profiling – Still in early stage
IHC and Molecular test accuracies a 92% and 95% with bloods much lower at this stage (2019)
For the purpose of discovering if you are a match for Check Point Immunotherapy, the IHC test is most logical. If via the IHC test you do not have the MSi-high as a biomarker then pursue the full “Molecular Profiling” to discover a full road map of you tumors make up and what mutations are driving your cancer. This can then be matched up with known treatments globally.