AIMS: Establishing mismatch repair (MMR) status of colorectal cancers is important to enable detection of underlying Lynch syndrome and inform prognosis and therapy. Current testing typically involves either PCR-based microsatellite (MSI) testing or MMR protein immunohistochemistry (IHC). We aimed to compare these two approaches in a large, population-based cohort of stage 2 and 3 colon cancer cases in Northern Ireland.
METHODS AND RESULTS: Using the Promega pentaplex assay, we determined MSI status to a four antibody MMR IHC panel. IHC was applied to tumour tissue microarrays with triplicate tumour sampling and assessed manually. Of 593 cases with available MSI and MMR IHC results, 136 (22.9%) were MSI-H and 135 (22.8%) displayed abnormal MMR IHC. Concordance was extremely high, with 97.1% of MSI-H cases showing abnormal MMR IHC and 97.8% of cases with abnormal IHC showing MSI-H status. Under-representation of tumour epithelial cells in samples from heavily inflamed tumours resulted in misclassification of several cases with abnormal MMR IHC as microsatellite stable. MMR IHC revealed rare cases with unusual patterns of MMR protein expression, unusual combinations of expression loss or secondary clonal loss of expression, further illustrated by repeat immunostaining on whole tissue sections.
CONCLUSIONS: MSI PCR testing and MMR IHC can be considered equally proficient tests for establishing MMR/MSI status, when aware of the potentials pitfalls of either method. Methodology choice may depend on available services and expertise.