{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:54:52Z","timestamp":1781776492449,"version":"3.54.5"},"reference-count":19,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2026,4,30]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>MLH1, MSH2, MSH6<\/jats:italic>\n                      and\n                      <jats:italic>PMS2<\/jats:italic>\n                      , (2) aiding MMR gene variant interpretation and (3) deciding on use of immune checkpoint blockade therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2019 final aggregated scores (FAS) for performance comparison.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 2011 and 2022,\u2009there 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2026-210695","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:20:28Z","timestamp":1779211228000},"page":"467-474","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["UK participation in the UK National External Quality Assessment Scheme for mismatch repair immunohistochemistry: insights from the last decade"],"prefix":"10.1136","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-628X","authenticated-orcid":false,"given":"Luke AR","family":"Farmkiss","sequence":"first","affiliation":[{"name":"Histopathology Department, Plymouth Hospitals NHS Foundation Trust, Derriford Hospital, Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-2362","authenticated-orcid":false,"given":"Andrew","family":"Dodson","sequence":"additional","affiliation":[{"name":"UK National External Quality Assessment Scheme ICC & ISH, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Parry","sequence":"additional","affiliation":[{"name":"UK National External Quality Assessment Scheme ICC & ISH, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9374-7465","authenticated-orcid":false,"given":"Michelle Charmaine","family":"James","sequence":"additional","affiliation":[{"name":"UK National External Quality Assessment Scheme ICC & ISH, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-0794","authenticated-orcid":false,"given":"Ian M","family":"Frayling","sequence":"additional","affiliation":[{"name":"Inherited Tumour Syndromes Research Group, Cancer & Genetics Division, School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6826-8770","authenticated-orcid":false,"given":"Mark Johan","family":"Arends","sequence":"additional","affiliation":[{"name":"Edinburgh Pathology, Institute of Genetics & Cancer, The University of Edinburgh College of Medicine and Veterinary Medicine, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"2026061802100677000_79.7.467.1","unstructured":"Idos G , Valle V , et al . Lynch syndrome. In: Adam MP , Bick S , Mirzaa GM , eds. GeneReviews, 1993-2026. Seattle (WA): University of Washington, Seattle, 2021. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1211\/"},{"key":"2026061802100677000_79.7.467.2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/path.5139","article-title":"Lynch syndrome - cancer pathways, heterogeneity and immune escape","volume":"246","author":"Seth","year":"2018","journal-title":"J Pathol"},{"key":"2026061802100677000_79.7.467.3","unstructured":"Frankel W , Arends MJ , Frayling IM , et al . Lynch syndrome, Chapter 14, genetic tumour syndromes of the digestive system. In: World Health Organization classification of tumours of the digestive system. 5th edition. Lyon, France: IARC Press, 2019: 515\u201321."},{"key":"2026061802100677000_79.7.467.4","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/path.5422","article-title":"Molecular pathology of Lynch syndrome","volume":"250","author":"Cerretelli","year":"2020","journal-title":"J Pathol"},{"key":"2026061802100677000_79.7.467.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0536-8"},{"key":"2026061802100677000_79.7.467.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.01.014"},{"key":"2026061802100677000_79.7.467.7","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2015-203083"},{"key":"2026061802100677000_79.7.467.8","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-015-1254-5","article-title":"A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients","volume":"15","author":"Snowsill","year":"2015","journal-title":"BMC Cancer"},{"key":"2026061802100677000_79.7.467.9","doi-asserted-by":"publisher","DOI":"10.3310\/hta18520"},{"key":"2026061802100677000_79.7.467.10","unstructured":"National Institute of Health and Clinical Excellence . Molecular testing strategies for Lynch syndrome in people with colorectal cancer. Diagnostics guidance [DG27]. 2017. Available: https:\/\/www.nice.org.uk\/guidance\/dg27 [Accessed 18 Aug 2018]."},{"key":"2026061802100677000_79.7.467.11","unstructured":"National Institute of Health and Clinical Excellence . Testing strategies for Lynch syndrome in people with endometrial cancer. Diagnostics guidance [DG42]. 2020. Available: https:\/\/www.nice.org.uk\/guidance\/dg42 [Accessed 14 Feb 2023]."},{"key":"2026061802100677000_79.7.467.12","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz116"},{"key":"2026061802100677000_79.7.467.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(99)00045-3"},{"key":"2026061802100677000_79.7.467.14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.6826"},{"key":"2026061802100677000_79.7.467.15","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-019-0738-1","article-title":"Mismatch repair deficiency\/microsatellite instability-high as a predictor for anti-PD-1\/PD-L1 immunotherapy efficacy","volume":"12","author":"Zhao","year":"2019","journal-title":"J Hematol Oncol"},{"key":"2026061802100677000_79.7.467.16","unstructured":"Loughrey M , Quirke P , Shepherd N . G049 standards and datasets for reporting cancers. Dataset for histopathological reporting of colorectal cancer Royal College of Pathologists. 2018. Available: https:\/\/www.rcpath.org\/static\/c8b61ba0-ae3f-43f1-85ffd3ab9f17cfe6\/G049-Dataset-for-histopathological-reporting-of-colorectal-cancer.pdf [Accessed 14 Feb 2023]."},{"key":"2026061802100677000_79.7.467.17","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/S1470-2045(23)00595-8","article-title":"Universal testing of cutaneous sebaceous carcinoma: a missed opportunity in Lynch syndrome detection","volume":"25","author":"Rajan","year":"2024","journal-title":"Lancet Oncol"},{"key":"2026061802100677000_79.7.467.18","first-page":"2596","article-title":"Distinct molecular profiles in Lynch syndrome-associated and sporadic ovarian carcinomas","volume":"133","author":"Niskakoski","year":"2013","journal-title":"Int J Cancer"},{"key":"2026061802100677000_79.7.467.19","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/jnci\/djad063","article-title":"Microsatellite instability in noncolorectal and nonendometrial malignancies in patients with Lynch syndrome","volume":"115","author":"Elze","year":"2023","journal-title":"J Natl Cancer Inst"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp-2026-210695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:11:38Z","timestamp":1781773898000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp-2026-210695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":19,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,6,18]]},"published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1136\/jcp-2026-210695"],"URL":"https:\/\/doi.org\/10.1136\/jcp-2026-210695","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]}}}