Hi all,
I firstly wanted to thank the community here. I'm posting for the first time, but I visit frequently to read about your experiences. It's been really helpful to gain knowledge and get some highly needed solidarity.
My dad's a metastatic rectal cancer patient. Chemo was pretty effective in the beginning, but the disease relapsed pretty soon after. Once we had exhausted the standard chemo lines of treatment (FOLFOX/FOLFIRI), we tried Regorafenib/Stivarga, but that hasn't helped stop the progression. Immunotherapy is the obvious next option, for which we need to be certain about his MSI status. We've had conflicting lab results, and we've not been able to get tissue for more testing, so I wanted some help to make help sense of this.
- A MSI test using the IHC technique was done on the tissue collected at the time of the original diagnosis. It reported MSI-H/dMMR, with MLH1, MSH2 and PMS2 markers not expressed, and only MSH6 expressed.
- Since this was a rare result, we sent the same tissue again for a MSI test using PCR. Both tissue and a blood sample were collected here. This reported MSS, with the markers BAT25, BAT26, NR21, NR22 and NR24 detected as stable.
- After this, we exhausted the primary tumor tissue as it seems to have grown inwards (extraluminary regions). The lung (and liver) mets were small and inaccessible, so we couldn't get tissue from those either.
- We'd done a ctDNA blood test, and that also reported MSS. However, I don't know how accurate the ctDNA tests are for assessing MSI status (the variant allele frequency in the blood sample was between 0.5 to 1%)
I had some queries:
- I wanted to know if someone has had a similar experience, i.e, conflicting MSI results?
- From what I've read, IHC looks for the proteins (the phenotype), and PCR/NGS would look at mutations in the gene sequence (genotype). Is it possible that one can be MMR deficient, but have the standard PCR markers stable?
- Any opinion about the case in general?
Our docs say that if we can't get new tissue, we should go by the PCR result as that's more accurate, but I didn't want us to rule out a potential line of treatment without being certain.
Thank you!