We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). The initial immunohistochemistry (IHC) test for deficient mismatch repair gave a false negative result. However, the same mutation has accurately been detected with IHC in other cancers with microsatellite instability (MSI). This supports the determining role of somatic missense mutations in MMR IHC. MSI-PCR testing confirmed MSI and the patient benefited from nivolumab with a complete metabolic response. We explain the rationale for immunotherapy in mCRC, current testing strategies and discuss future developments in MSI testing. We advocate for upfront testing using both IHC and MSI-PCR to direct therapy in mCRC, and a greater understanding of IHC and MSI-PCR testing pitfalls.
Keywords: Lynch syndrome; colorectal carcinoma; diagnostic errors; immune checkpoint inhibitors; immunohistochemistry; microsatellite instability.
Bowel cancer that has spread is a serious condition that will often lead to loss of life. There is a new treatment called immunotherapy which helps extend the life of people with cancer that has spread beyond the bowel, but it does not work for everyone. Immunotherapy works best for people whose tumors have lost the ability to repair DNA. People with Lynch syndrome often have these types of tumors because they are born with an inherited predisposition for faulty DNA repair. We treated a patient with Lynch syndrome and bowel cancer, and wanted to use immunotherapy, but the test we used failed to give the right result. We think this is because the test is not very good at picking up unusual types of mutations that can occur and that using another test as well will prevent this mistake from happening to others.