[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-337676-105":59,"doc-detail-337676-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","microsatellite-instability-and-mismatch-repair-protein-deficiency-equal-predictive-markers","Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?","","Current clinical practice recommends mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) testing as predictive markers for immune checkpoint inhibitor therapies. International guidelines often treat MMR IHC as the gold standard and consider MSI mainly in special situations or to screen for Lynch syndrome. Literature reports differing dMMR and MSI rates across cancer types, frequent discrepancies between assays, and distinct immunotherapy efficacy when patient selection uses dMMR versus MSI status. These findings challenge the assumption that dMMR and MSI are equivalent predictive markers.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/microsatellite-instability-and-mismatch-repair-protein-deficiency-equal-predictive-markers/337676/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/microsatellite-instability-and-mismatch-repair-protein-deficiency-equal-predictive-markers/337676.png","ImageObject",300,407,{"name":92,"@type":93},"Emma Wilson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What do current guidelines recommend for predicting immunotherapy response in cancers with mismatch repair deficiency?","Question",{"text":113,"@type":114},"Guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers for immune checkpoint inhibitor therapies.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why might MMR IHC and molecular MSI tests not be equivalent predictive markers?",{"text":118,"@type":114},"The review describes literature showing different rates of deficient MMR (dMMR) and MSI across cancer types, and frequent discrepancies between the two testing approaches, especially in certain non-colorectal/non-endometrial cancers and unusual dMMR phenotypes.",{"name":120,"@type":111,"acceptedAnswer":121},"How do differences in diagnostic testing influence patient selection for immune checkpoint inhibitors?",{"text":122,"@type":114},"Scattered clinical data indicate that immune checkpoint inhibitor efficacy can differ depending on whether patient selection is based on dMMR status versus MSI status.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},337676,1790095461,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":41},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","TYPE Review  \nPUBLISHED 09 April 2024  \nDOI 10.3389/pore.2024.1611719  \nOPEN ACCESS  \nEDITED BY  \nAndrea Ladányi,  \nNational Institute of Oncology (NIO), Hungary  \n*CORRESPONDENCE  \nJózsef Tímár,  \n [jtimar@gmail.com](jtimar@gmail.com)  \nRECEIVED 05 February 2024  \nACCEPTED 27 March 2024  \nPUBLISHED 09 April 2024  \nCITATION  \nNádorvári ML, Lotz G, Kulka J, Kiss A and Tímár J (2024), Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?  \nPathol. Oncol. Res. 30:1611719 .  \ndoi: 10.3389/pore.2024.1611719  \nCOPYRIGHT  \n© 2024 Nádorvári, Lotz, Kulka, Kiss and Tímár. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nMicrosatellite instability and mismatch repair protein deficiency: equal predictive markers?  \nMaja L. Nádorvári, Gábor Lotz, Janina Kulka, András Kiss and József Tímár*  \nDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary  \nCurrent clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. For example, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHCand MSI tests, especially in non-colorectal and non-endometrial cancers and in cases with unusual dMMR phenotypes. There are also scattered clinical data showing that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and genetic MSI status are equal predictive markers of the immunotherapies.  \nKEYWORDS  \nmismatch repair deficiency, microsatellite instability, immunohistochemistry, molecular testing, cancer  \nIntroduction  \nMMR deficiency (dMMR), and the resultant microsatellite instability (MSI), is one of the most frequent genetic alterations of the DNA repair systems of cancer. It is most prevalent in the gastrointestinal (GI) tract (colorectal, gastric, and esophageal) and endometrial cancers but can occur at a much lower frequency in any other cancer types. Initially, they served only as a genetic marker for the hereditary cancer disease Lynch syndrome [1, 2], but now most tests for microsatellite instability are performed as predictive marker tests of immune checkpoint inhibitor (ICI) therapies [3–7] . Currently, the two main diagnostic methods of microsatellite instability are testing the expression of MMR proteins with immunohistochemistry (IHC) and molecular diagnostics of MSI  \nPathology & Oncology Research 01 Published by Frontiers  \nmostly by polymerase chain reaction (PCR)-based techniques. Next-generation sequencing (NGS)-based detection has also become a tool to determine MSI status, as it can analyze more microsatellite markers and MMR gene mutations simultaneously, which can help in therapeutic decisions [8] . Immunohistochemistry can only reveal the absence of MMR proteins, which is excellent for Lynch syndrome. However, IHC cannot test the mismatch repair system from a functional aspect, which is a crucial factor in immune che","cbCaioHEF9E9V2w3","https://ap.wps.com/l/cbCaioHEF9E9V2w3","pdf",1090591,12,"English","# Introduction\n# Mismatch repair deficiency and resultant microsatellite instability","[{\"question\":\"What do current guidelines recommend for predicting immunotherapy response in cancers with mismatch repair deficiency?\",\"answer\":\"Guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers for immune checkpoint inhibitor therapies.\"},{\"question\":\"Why might MMR IHC and molecular MSI tests not be equivalent predictive markers?\",\"answer\":\"The review describes literature showing different rates of deficient MMR (dMMR) and MSI across cancer types, and frequent discrepancies between the two testing approaches, especially in certain non-colorectal/non-endometrial cancers and unusual dMMR phenotypes.\"},{\"question\":\"How do differences in diagnostic testing influence patient selection for immune checkpoint inhibitors?\",\"answer\":\"Scattered clinical data indicate that immune checkpoint inhibitor efficacy can differ depending on whether patient selection is based on dMMR status versus MSI status.\"}]","Microsatellite instability and mismatch repair protein deficiency: equal predictive markers? | PDF",1790020096]