[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-351074-105":59,"doc-detail-351074-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","low-microsatellite-instability-revisited-a-review","Low microsatellite instability revisited - a review","","Microsatellite instability (MSI), driven by impaired mismatch repair (MMR), is a biomarker used to predict responses to immune checkpoint inhibitors across cancers. While MSI-high tumors show extensive instability across many loci, low-level MSI (MSI-L) involves instability at few loci and remains controversial. Evidence from colorectal and gastric cancers suggests MSI-L can associate with worse prognosis, therapy-related mutational burden changes, and distinct chemotherapy responses, potentially linked to dinucleotide repeat instability and DNA damage tolerance pathways. This review compares diagnostic methods, summarizes clinical and molecular findings, and evaluates therapeutic vulnerability.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/low-microsatellite-instability-revisited-a-review/351074/",{"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/low-microsatellite-instability-revisited-a-review/351074.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-25","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What distinguishes MSI-L from MSI-H in tumors?","Question",{"text":112,"@type":113},"MSI-H reflects widespread instability across many microsatellite loci, whereas MSI-L refers to instability at a low number of loci and is less well defined and debated.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is MSI-L considered controversial?",{"text":117,"@type":113},"Ambiguity arises largely from methodological inconsistencies, including different marker panels, cut-off values, and detection platforms, which can lead to varying classification and results.",{"name":119,"@type":110,"acceptedAnswer":120},"What clinical associations have been reported for MSI-L in gastric and colorectal cancers?",{"text":121,"@type":113},"Studies report that MSI-L, especially when defined by dinucleotide repeat instability, may correlate with poorer prognosis and altered chemotherapy response, including increased tumor mutational burden after chemotherapy and better response to platinum/5-fluorouracil-based neoadjuvant treatment.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},351074,1790378839,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Virchows Archiv (2026) 488:215–228  \n[https://doi.org/10.1007/s00428-026-04400-w](https://doi.org/10.1007/s00428-026-04400-w)  \nLow microsatellite instability revisited: a review  \nBianca Grosser1,2 · Meike Kohlruss1 · Gisela Keller1  \nReceived: 15 October 2025 / Revised: 12 December 2025 / Accepted: 6 January 2026 / Published online: 21 January 2026 © The Author(s) 2026  \nAbstract  \nMicrosatellite instability (MSI), caused by impaired mismatch repair (MMR), has gained prominence as a biomarker predicting response to immune checkpoint inhibitors in various cancers. MSI-high (MSI-H) tumours exhibit widespread instability across multiple microsatellite loci and are well-characterized. In contrast, low-level microsatellite instability (MSI-L)—marked by instability at a low number of loci—is poorly understood and its biological relevance remains controversial. MSI-L has often been grouped together with microsatellite stable (MSS) tumours, given the lack of consistent molecular distinctions. However, some studies, particularly in colorectal and gastric cancers, have reported that MSI-L correlates with distinct clinical and molecular features, including poorer prognosis, increased tumour mutational burden (TMB) following chemotherapy, and better response to platinum/5-fluorouracil-based neoadjuvant chemotherapy. Notably, these associations frequently involve instability at dinucleotide repeat markers, hinting at a specific subset of MSI-L. Moreover, recent data provide initial evidence that MSI-L may be associated with subtle alterations of genes involved in DNA damage tolerance pathways. This review aims to clarify the current understanding of MSI-L by (a) comparing diagnostic methods and their influence on MSI-L classification,(b) summarizing clinical and molecular associations of MSI-L specifically in gastric and colorectal cancer,(c) highlighting new aspects regarding potential mechanisms underlying MSI-L, focusing on the particular unstable marker and a possible role of the DNA damage tolerance pathways, and (d) discussing whether MSI-L, particularly defined by dinucleotide repeat instability, may serve as a marker for therapeutic vulnerability.  \nKeywords Microsatellite instability · Gastric carcinoma · Colorectal cancer · Dinucleotide repeats · Chemotherapy response · Biomarker  \nIntroduction  \nMicrosatellite instability (MSI) is characterized by insertions or deletions in repetitive DNA sequences within a tumour, resulting from defects in the mismatch repair (MMR) system. The key players of this system are the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 . MSI testing plays a critical role in predicting responses to immune checkpoint inhibitors in various cancers, particularly colorectal and gastric carcinomas [1, 2] . MSI in this context is usually characterized by a high level of unstable microsatellite markers  \n* Gisela Keller [gisela.keller@tum.de](gisela.keller@tum.de)  \n1 Institute of Pathology, TUM School of Medicine and Health, Technical University of Munich, Trogerstr. 18, 81675 Munich, Germany  \n2 Institute of Pathology and Molecular Diagnostics, University Hospital Augsburg, Augsburg, Germany  \nin the tumour and is also referred to as high MSI (MSI-H) . These tumours are characterized by high mutational burden, distinct molecular profiles, and favourable responses to immunotherapy. In contrast, tumours showing instability ata low number of loci are classified as MSI-low (MSI-L), a category that remains poorly defined and is controversially discussed [3–5] .  \nMSI can be determined by various methods that differ in their accuracy, sensitivity, and application. We believe that the ambiguity surrounding MSI-L arises largely from methodological inconsistencies. Different microsatellite marker panels, cut-off values, and detection platforms ([e.g. PCR vs. next-generation sequencing](e.g. PCR vs. next-generation sequencing)) produce varying results. Furthermore, the lack of a consistent molecular signature has fuel","cbCaiffPbBQHmBqJ","https://ap.wps.com/l/cbCaiffPbBQHmBqJ","pdf",1870185,14,"English","# Abstract\n# Introduction\n## MSI determination and MSI-L definition\n# Polymerase chain reaction (PCR)-based assay\n# Methods and diagnostic comparison\n# Clinical and molecular associations in gastric and colorectal cancer\n# Mechanistic hypotheses and DNA damage tolerance pathways\n# Therapeutic vulnerability of MSI-L","[{\"question\":\"What distinguishes MSI-L from MSI-H in tumors?\",\"answer\":\"MSI-H reflects widespread instability across many microsatellite loci, whereas MSI-L refers to instability at a low number of loci and is less well defined and debated.\"},{\"question\":\"Why is MSI-L considered controversial?\",\"answer\":\"Ambiguity arises largely from methodological inconsistencies, including different marker panels, cut-off values, and detection platforms, which can lead to varying classification and results.\"},{\"question\":\"What clinical associations have been reported for MSI-L in gastric and colorectal cancers?\",\"answer\":\"Studies report that MSI-L, especially when defined by dinucleotide repeat instability, may correlate with poorer prognosis and altered chemotherapy response, including increased tumor mutational burden after chemotherapy and better response to platinum/5-fluorouracil-based neoadjuvant treatment.\"}]","Low microsatellite instability revisited - a review | PDF",1790092494,35]