MSS and MSI-H: Something every CRC patient should know

It is very important for anyone diagnosed with colorectal cancer to know whether the cancer is MSS or MSI-H. Here is a quick summary of why this matters.

  1. MSS is the “normal” state of our cells where the MisMatch Repair (MMR) pathway is active and functional. MSS CRC is the most common type; about 85% of all stage CRC and about 96% of stage 4 CRC is MSS. This is also the more challenging kind of CRC to treat, but there is some strength in numbers as everyone is looking for new ways to treat MSS CRC.
  2. MSI is the “mutant” state where the MMR pathway is non-functional. MSI-H CRC is about 15% of all CRC and about 4% of stage 4 CRC.The good news is that this subset of CRC can be treated with a kind of treatment known as immunotherapy, which can be curative.

How to know if your tumor is MSS or MSI from a pathology report

In most cases, biopsy or tumor samples are examined by a pathology lab using immunohistochemistry (IHC) (they look for protein expression on slides of the biopsy or tumor).

The report that comes back may read something like this:

  • MLHI : Intact nuclear expression (expressed)
  • MSH2 : Intact nuclear expression (expressed)
  • MSH6 : Intact nuclear expression (expressed)
  • PMS2 : Intact nuclear expression (expressed)
  • No loss of nuclear expression of MMR proteins, low probability of MSI-H

This means that your tumor is MSS (microsatellite stable). The statement that there is a “low probability of MSI-H” refers to the rare case where, despite having no loss of nuclear expression of MMR proteins that can be detected by IHC, there can be a defect in the gene that is detectable. For the majority of people, the statement above means they are MSS, even though the report does not explicitly state that.