UK participation in the UK National External Quality Assessment Scheme for mismatch repair immunohistochemistry: insights from the last decade

Aim Comparison of immunohistochemical detection of mismatch repair (MMR) proteins within tumours, as deficient MMR is important for (1) the detection of Lynch Syndrome, caused by inherited variants affecting the DNA MMR genes MLH1, MSH2, MSH6 and PMS2 , (2) aiding MMR gene variant interpretation and (3) deciding on use of immune checkpoint blockade therapy. Methods This retrospective analysis compares the performance of different MMR immunohistochemistry (IHC) antibody clones, detection systems and automation IHC platforms using a decade of technical data submitted to the UK National External Quality Assessment Scheme (NEQAS) as part of its MMR EQA programme, with calculation of participants’ final aggregated scores (FAS) for performance comparison. Results Between 2011 and 2022, there were 38 MMR assessment runs, with an average of 44.8 submissions per antigen per assessment run. MMR module participation greatly increased over this decade. Average FAS showed a small non-significant upward trend with the lowest scores (14.6) observed in the first half of the decade, with greater concordance between FAS scores (15.1) in the second half of the decade. For MMR IHC, the antibody clones most frequently used were M1 and ES05 (FAS 15.7 and 15.1) for MLH1, G219-1129 and FE11 (FAS 14.8 and 14.1) for MSH2, EP51 and A16-4 (FAS 15.2 and 15.2) for PMS2 and SP93 and EP49 (FAS 16.1 and 15.6) for MSH6. The most common detection systems were Ventana Optiview, Leica BondMax, Leica Bond Refine, Dako FLEX+ and Ventana UltraView. Conclusions The quality of submitted MMR IHC sections has risen, with recent assessment scores showing lower variability, indicating better antibody clone performance, improved detection systems and IHC automation platform technology, allied to increasing technical competence among participants. UK NEQAS provides insight and feedback relating to MMR IHC protocols that most reliably produce high-quality MMR IHC staining to facilitate accurate reporting of the increasingly important tumour MMR status.