Is my tumor MSS (pMMR) or MSI-H (dMMR)?
All newly diagnosed CRC patients should have their tumors tested for MSS/MSI status. Finding out which kind of tumor you have can have a big impact on what treatment options are available to you.
So what do those acronyms really mean? Learning about mismatch repair (MMR) is a great place to start.
There are two major types of colon cancer:
- Microsatellite stable (MSS) or proficient mismatch repair (pMMR) is the “normal” state our cells are in, where the mismatch repair (MMR) pathway is active and functional. MMR is the body’s system for recognizing and repairing wrong letters in DNA synthesis. MSS is the most common kind of colon cancer.
- Microsatellite instability (MSI) or deficient mismatch repair (dMMR) is the “mutant” state, where the MMR pathway is not working as usual. This is often called MSI-H for microsatellite instability high.
So what are microsatellites?
Microsatellites are short, repeated sequences in your DNA. They can vary in length between people, but within one person’s DNA they are a specific length. We can use this as a kind of “fingerprint” of someone’s DNA.
Here’s what they look like:
When your cells grow and divide, your DNA needs to replicate too. As we mentioned earlier, your body can make mistakes! So DNA mismatch repair enzymes — proteins with special jobs — come along and fix any errors. These enzymes are coded for in your DNA itself.
Now, there can be an issue where the enzymes used to repair your DNA are themselves defective. If this happens, those short repeated sequences, microsatellites, can accumulate errors in length and get wonky. If your microsatellites have these errors, your tumor is likely MSI-H.
How do I know if my MMR pathway is working normally?
Most cancer centers send a sample of your tumor, called a biopsy, to their pathology department for MMR studies using an immunohistochemistry (IHC) study. Through this process, doctors look at your tumor’s protein expression on microscope slides.
You might get a pathology report that says something like this:
MLH1: Intact nuclear expression (or expressed, positive or present)
MSH2: Intact nuclear expression (or expressed, positive or present)
MSH6: Intact nuclear expression (or expressed, positive or present)
PMS2: Intact nuclear expression (or expressed, positive or present)
This means you are MSS. These acronyms (MLH1, MSH2, MSH6, PMS2) are all specific proteins involved in mismatch repair, and the report shows they are all present as they should be.
Your report might go on to say:
No loss of nuclear expression of MMR proteins (or negative or absent), low probability of MSI-H.
This statement also means that your tumor is MSS. When it says there’s a “low probability of MSI-H,” the report refers to the rare case where — despite having no loss of the MMR proteins — there can be a defect in the gene. For the great majority of people, the statement above means that they are MSS — even if the report does not explicitly state that!
You might also get a pathology report that looks like this:
MLH1: Intact nuclear expression (or expressed)
MSH2: Intact nuclear expression (or expressed)
MSH6: Loss of nuclear expression (or not expressed)
PMS2: Intact nuclear expression (or expressed)
This means that you are MSI. Your pathology report might go on to say, for example:
Loss of nuclear expression for MSH6 only. High probability of Lynch syndrome (tumor MSI evaluation and sequencing of germline MSH6 are indicated).
Lynch syndrome is a hereditary disease linked to a higher risk of cancer.
Want to learn more about Lynch syndrome?
Check out this link from the Mayo Clinic.
Don’t worry, we’ll talk more about Lynch syndrome later on.
So what does all of this mean for treatment?
The great majority of all CRC is MSS. About 85% of all-stage CRC and about 96% of stage IV CRC is MSS.
MSI makes up about 15% of all CRC and about 4% of stage IV CRC. The good news is that this subset of CRC can be treated with immunotherapy, which is very effective for some patients.
This is why it’s so important that everyone diagnosed with CRC knows whether their tumor is MSS or MSI!
Looking for more information about what MSS/ MSI-H status means for your treatment?
Come join us in Colontown!
- In Tom’s MSI-H Clinic, you can learn all about clinical trials and treatment options specific to MSI-H patients
- In Tom’s MSS Clinical Trials Clinic, you can learn about clinical trials open to MSS patients
Interested in joining? Fill out the registration form here.