[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-339537-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-339537-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","molecular-classification-of-gastrointestinal-and-pancreatic-neuroendocrine-neoplasms-are-we-ready-for-that","Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?","","Increasing availability of molecular analysis technologies over the past two decades has clarified genomic alterations in gastrointestinal and pancreatic neuroendocrine neoplasms (NEN). These findings have reinforced and refined pathological classification by distinguishing neuroendocrine carcinomas (NEC) from neuroendocrine tumors (NET) and supporting definition of the G3 NET category. Differential gene mutations, structural abnormalities, and epigenetic changes also reveal candidate precision-therapy molecular targets. This review summarizes molecular features, links them to pathological and clinical traits, and evaluates their value as predictive biomarkers, assessing feasibility and applicability of molecular classification for digestive NEN.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/molecular-classification-of-gastrointestinal-and-pancreatic-neuroendocrine-neoplasms-are-we-ready-for-that/339537/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/molecular-classification-of-gastrointestinal-and-pancreatic-neuroendocrine-neoplasms-are-we-ready-for-that/339537.png","ImageObject",300,407,{"name":42,"@type":43},"Violet","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How have molecular analyses influenced the classification of gastrointestinal and pancreatic neuroendocrine neoplasms (NEN)?","Question",{"text":63,"@type":64},"They reveal genomic alterations that support and refine pathological classification, clarifying differences between NEC and NET and helping define the G3 NET category.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What molecular differences have been identified between NEC and NET, and why do they matter?",{"text":68,"@type":64},"Gene mutations, structural abnormalities, and epigenetic changes differ between NEC and NET, identifying potential molecular targets for precision therapy.",{"name":70,"@type":61,"acceptedAnswer":71},"How is Ki67 used in stratifying risk within NET, and what limits its role in some settings?",{"text":72,"@type":64},"Ki67 PI has been validated for digestive NET using a three-tier grading system; its prognostic role is well established in pancreatic NET but less defined in NET from other primary sites.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},339537,1790832353,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":108},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","Endocrine Pathology (2024) 35:91–106  \n[https://doi.org/10.1007/s12022-024-09807-2](https://doi.org/10.1007/s12022-024-09807-2)  \nMolecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?  \nSilvia Uccella1,2  \nAccepted: 29 February 2024 / Published online: 12 March 2024 © The Author(s) 2024  \nAbstract  \nIn the last two decades, the increasing availability of technologies for molecular analyses has allowed an insight in the genomic alterations of neuroendocrine neoplasms (NEN) of the gastrointestinal tract and pancreas. This knowledge has confirmed, supported, and informed the pathological classification of NEN, clarifying the differences between neuroendocrine carcinomas (NEC) and neuroendocrine tumors (NET) and helping to define the G3 NET category. At the same time, the identification genomic alterations, in terms of gene mutation, structural abnormalities, and epigenetic changes differentially involved in the pathogenesis of NEC and NET has identified potential molecular targets for precision therapy. This review critically recapitulates the available molecular features of digestive NEC and NET, highlighting their correlates with pathological aspects and clinical characteristics of these neoplasms and revising their role as predictive biomarkers for targeted therapy. In this context, the feasibility and applicability of a molecular classification of gastrointestinal and pancreatic NEN will be explored.  \nKeywords Neuroendocrine neoplasm · Neuroendocrine tumor · Neuroendocrine carcinoma · Molecular classification · Target therapy · Genetics  \nIntroduction  \nThe definition and classification of neuroendocrine neoplasms (NEN) have been subject to ongoing refinement for the last years. On one hand, the distinction between neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC), supported by histopathological features, molecular hallmarks, and clinical evidence, has provided a solid base for therapeutic management [1, 2] . On the other hand, the“NEN concept” has been discussed for neoplastic proliferations arising outside the “classic” thoracic and digestive sites, with different outcomes. For instance, the nomenclature shift from pituitary adenoma to pituitary neuroendocrine tumorPitNET has acknowledged the morpho-functional properties of these neoplasms and has also taken in account their  \n* Silvia Uccella  \n[silvia.uccella@hunimed.eu](silvia.uccella@hunimed.eu); [silvia.uccella@gmail.com](silvia.uccella@gmail.com)  \n1 Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy  \n2 Pathology Service IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy  \nclinical correlates, in terms of both endocrine function and oncological manifestations [3, 4] . In contrast, for breast cancers, the application of the “NEN concept” has not proven tobe completely justified by well-defined morphological and biological characteristics and, as a matter of fact, is not useful in terms of patient management, at least at the present moment [5–7]. In general, the definition and the classification of NENs are currently based on well-established morphological criteria, supported by the expression of specific general neuroendocrine markers (synaptophysin, chromogranin A, and INSM1), and related with predictable clinical behavior and response to therapy [8] . These concepts have been clarified in the latest edition of the WHO classification of neuroendocrine neoplasms and have been extended to extrathoracic and extra-digestive primary sites [8] . The application of this classification framework in real-life series is needed to validate this approach in so-called “unusual sites” of NENs, namely, the urinary tract, the female and male genital systems, and the head and neck region.  \nThe cornerstone of the current classification scheme of NEN in every primary anatomical location is the identification of the morphol","cbCaiadOVmebylZC","https://ap.wps.com/l/cbCaiadOVmebylZC","pdf",1354645,16,"English","# Abstract\n## Keywords\n# Introduction\n## Neuroendocrine neoplasms: evolving definitions and classification\n## Morphological differentiation and clinical implications\n## Molecular mechanisms and therapeutic targets\n## Grading systems and Ki67 role","[{\"question\":\"How have molecular analyses influenced the classification of gastrointestinal and pancreatic neuroendocrine neoplasms (NEN)?\",\"answer\":\"They reveal genomic alterations that support and refine pathological classification, clarifying differences between NEC and NET and helping define the G3 NET category.\"},{\"question\":\"What molecular differences have been identified between NEC and NET, and why do they matter?\",\"answer\":\"Gene mutations, structural abnormalities, and epigenetic changes differ between NEC and NET, identifying potential molecular targets for precision therapy.\"},{\"question\":\"How is Ki67 used in stratifying risk within NET, and what limits its role in some settings?\",\"answer\":\"Ki67 PI has been validated for digestive NET using a three-tier grading system; its prognostic role is well established in pancreatic NET but less defined in NET from other primary sites.\"}]","Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That? | PDF",1790030871]