Immunochemistry screening for Lynch syndrome in colorectal adenocarcinoma using an initial two antibody panel can replace a four antibody panel.

Aim: The current practice in immunochemistry staining for Lynch syndrome (LS) is to use a four-antibody panel, (MLH1, MSH2, MSH6, PMS2) to screen for the four Mismatch Repair (MMR) gene expressions involved. We hypothesised that testing two antibodies (MSH6 and PMS2), followed by the other two only when there is loss of expression of the first two antibodies, would be equally effective as a four antibody panel in detecting LS. This hypothesis is based on the biochemical binding properties of the MMR proteins.

Methods: We tested this hypothesis on a patient cohort consisting of all cases of colorectal cancer that were stained for MMR gene expression at Auckland City Hospital (Auckland, New Zealand) from the years 2000 to 2010 (inclusive), providing a series of 410 cases for this study. Exclusions were made based on heterogeneous staining pattern and unsatisfactory staining results on MSH6 and PMS2, which left n=400 included in the study.

Results: The MMR gene protein stains were regarded as demonstrating loss of expression (LOE) when there was no uptake in the nucleus of the tumour cells, with a positive internal control. The results from our analysis supported our hypothesis. Seventy-four cases showed LOE of MSH6 or PMS2. One of them showed LOE of all four MMR proteins. For the remaining 326 cases, there was no LOE of all four MMR proteins.

Conclusion: Our study gives further evidence that an initial two-antibody panel consisting of PMS2 and MSH6 would be as effective as a four-antibody panel in detecting DNA MMR gene protein LOE. This study has implications for significant cost cutting and improved efficiency in detection of DNA MMR gene protein LOE in LS.