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Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy
INTRODUCTION: Mismatch repair immunohistochemistry (MMR IHC) or microsatellite instability (MSI) testing is now routinely performed in patients with colorectal cancer (CRC) to select those requiring Lynch syndrome testing. MMR IHC is also carried out on CRC and upper gastrointestinal (GI) cancers to...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415243/ https://www.ncbi.nlm.nih.gov/pubmed/36018445 http://dx.doi.org/10.1007/s12029-022-00859-3 |
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author | R., Openshaw M. J., Williams T., Foo C., Moss A., Wotherspoon N., Starling. Z., Kemp |
author_facet | R., Openshaw M. J., Williams T., Foo C., Moss A., Wotherspoon N., Starling. Z., Kemp |
author_sort | R., Openshaw M. |
collection | PubMed |
description | INTRODUCTION: Mismatch repair immunohistochemistry (MMR IHC) or microsatellite instability (MSI) testing is now routinely performed in patients with colorectal cancer (CRC) to select those requiring Lynch syndrome testing. MMR IHC is also carried out on CRC and upper gastrointestinal (GI) cancers to select patients for immunotherapy. We review the Royal Marsden Hospital’s pathway of molecular to germline testing for Lynch syndrome in the context of NICE guidance and the National Test Directory. METHODS: We conducted (i) a retrospective audit of adherence to NICE guidance DG27 for patients diagnosed with CRC March 2017–August 2018 and (ii) a retrospective service evaluation of MMR IHC/Lynch syndrome testing in patients diagnosed with upper GI cancers January 2019–2020. RESULTS: Of 394 patients with CRC, 346 (87.8%) had MMR IHC testing. Thirty-eight of 346 (10.9%) were MMR deficient (MMR-D) and 5 (1.4%) were found to have pathogenic germline variants causing Lynch syndrome. Of 405 patients with upper GI cancers, 221 (54.6%) had MMR IHC testing. Ten of 221 (4.5%) were MMR-D and 1 (0.5%) had a pathogenic germline variant causing Lynch syndrome. DISCUSSION: This study highlights the small but significant number of patients, with CRC or upper GI cancers, which were caused by Lynch syndrome. It also highlights weaknesses in our testing pathway that limit access to germline testing. As MMR testing increases, it is important that clinicians are aware that patients with MMR-D tumours require reflex somatic testing or referral for germline testing. We have incorporated the guidelines into a pathway for use in clinics and multidisciplinary teams. |
format | Online Article Text |
id | pubmed-9415243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-94152432022-08-26 Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy R., Openshaw M. J., Williams T., Foo C., Moss A., Wotherspoon N., Starling. Z., Kemp J Gastrointest Cancer Original Research INTRODUCTION: Mismatch repair immunohistochemistry (MMR IHC) or microsatellite instability (MSI) testing is now routinely performed in patients with colorectal cancer (CRC) to select those requiring Lynch syndrome testing. MMR IHC is also carried out on CRC and upper gastrointestinal (GI) cancers to select patients for immunotherapy. We review the Royal Marsden Hospital’s pathway of molecular to germline testing for Lynch syndrome in the context of NICE guidance and the National Test Directory. METHODS: We conducted (i) a retrospective audit of adherence to NICE guidance DG27 for patients diagnosed with CRC March 2017–August 2018 and (ii) a retrospective service evaluation of MMR IHC/Lynch syndrome testing in patients diagnosed with upper GI cancers January 2019–2020. RESULTS: Of 394 patients with CRC, 346 (87.8%) had MMR IHC testing. Thirty-eight of 346 (10.9%) were MMR deficient (MMR-D) and 5 (1.4%) were found to have pathogenic germline variants causing Lynch syndrome. Of 405 patients with upper GI cancers, 221 (54.6%) had MMR IHC testing. Ten of 221 (4.5%) were MMR-D and 1 (0.5%) had a pathogenic germline variant causing Lynch syndrome. DISCUSSION: This study highlights the small but significant number of patients, with CRC or upper GI cancers, which were caused by Lynch syndrome. It also highlights weaknesses in our testing pathway that limit access to germline testing. As MMR testing increases, it is important that clinicians are aware that patients with MMR-D tumours require reflex somatic testing or referral for germline testing. We have incorporated the guidelines into a pathway for use in clinics and multidisciplinary teams. Springer US 2022-08-26 /pmc/articles/PMC9415243/ /pubmed/36018445 http://dx.doi.org/10.1007/s12029-022-00859-3 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Research R., Openshaw M. J., Williams T., Foo C., Moss A., Wotherspoon N., Starling. Z., Kemp Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy |
title | Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy |
title_full | Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy |
title_fullStr | Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy |
title_full_unstemmed | Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy |
title_short | Mismatch Repair Screening of Gastrointestinal Cancers: The Impact on Lynch Syndrome Detection and Immunotherapy |
title_sort | mismatch repair screening of gastrointestinal cancers: the impact on lynch syndrome detection and immunotherapy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415243/ https://www.ncbi.nlm.nih.gov/pubmed/36018445 http://dx.doi.org/10.1007/s12029-022-00859-3 |
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