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This study evaluates 5-hydroxymethylcytosine (5hmC) in 318 thyroid tumors using immunohistochemistry. Significant correlations are reported between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology, with intensity associations also involving focality and extrathyroidal extension. Higher 5hmC appears in follicular/oncocytic adenomas, while TERT promoter mutations show lower values and RAS mutations relate to higher expression.",{"@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/the-role-of-5-hydroxymethylcytosine-as-a-potential-epigenetic-biomarker-in-a-large-series-of-thyroid-neoplasms/327156/",{"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/the-role-of-5-hydroxymethylcytosine-as-a-potential-epigenetic-biomarker-in-a-large-series-of-thyroid-neoplasms/327156.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does 5hmC play in cancer biology according to the study?","Question",{"text":112,"@type":113},"5hmC is derived from 5-methylcytosine oxidation and has been implicated as a malignancy marker because its depletion is reported across various human cancers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was 5hmC expression measured in thyroid tumors?",{"text":117,"@type":113},"5hmC expression levels were evaluated by immunohistochemistry in a cohort of 318 thyroid tumors.",{"name":119,"@type":110,"acceptedAnswer":120},"Which tumor features are associated with 5hmC staining extension and intensity?",{"text":121,"@type":113},"Extension scores correlate with nodule size, vascular invasion, and oncocytic morphology, while intensity is associated with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology.","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},327156,1790482960,{"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":39,"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,"preview_page_count":4},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Endocrine Pathology (2024) 35:25–39  \n[https://doi.org/10.1007/s12022-024-09800-9](https://doi.org/10.1007/s12022-024-09800-9)  \nThe Role of 5‑Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms  \nSule Canberk1,2,3 · João Gonçalves1,2,4 · Elisabete Rios5 · Antónia A. Povoa6 · Ebru Tastekin7 ·  \nManuel Sobrinho‑Simões1,2,4,5 · Aysun Uguz8 · Ozlem Aydin9 · Umit Ince9 · Paula Soares1,2,4,5 · Valdemar Máximo1,2,4,5  \nAccepted: 16 January 2024 / Published online: 29 January 2024 © The Author(s) 2024  \nAbstract  \nCytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/ oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC) . TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS (H, N, or K) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.  \nKeywords Thyroid tumors · Hürthle cell tumor · Oncocytic cell tumors · Epigenetics · 5hmC  \nSule Canberk and João Gonçalves equally contributed to the study.  \n* Valdemar Máximo[vmaximo@ipatimup.pt](vmaximo@ipatimup.pt)  \n1 Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal  \n2 Institute of Molecular Pathology and Immunology  \nof the University of Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal  \n3 Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal  \n4 Faculty of Medicine of the University of Porto (FMUP), Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal  \n5 Department of Pathology, Faculty of Medicine  \nof the University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal  \n6 Department of General Surgery, Centro Hospitalarde Vila Nova de Gaia/Espinho (CHVNG/E), 4434-502 Vila Nova de Gaia, Portugal  \n7 Medical Faculty, Department of Pathology, Trakya University, Edirne, Turkey  \n8 Medical Faculty, Department of Pathology, Çukurova University, Adana, Turkey  \n9 Department of Pathology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey  \nIntroduction  \nAlterations in global 5hmC levels have emerged as an epigenetic marker of cancer. The loss of 5hmC has already been reported in some cancer models, such as melanoma, brain tumors, hematologic malignancies and bile duct, lung, ovarian, and hepatocellular carcinomas, as it acts asa p","cbCaiartucX7bcM6","https://ap.wps.com/l/cbCaiartucX7bcM6","pdf",1705971,15,"English","# Abstract\n## Introduction","[{\"question\":\"What role does 5hmC play in cancer biology according to the study?\",\"answer\":\"5hmC is derived from 5-methylcytosine oxidation and has been implicated as a malignancy marker because its depletion is reported across various human cancers.\"},{\"question\":\"How was 5hmC expression measured in thyroid tumors?\",\"answer\":\"5hmC expression levels were evaluated by immunohistochemistry in a cohort of 318 thyroid tumors.\"},{\"question\":\"Which tumor features are associated with 5hmC staining extension and intensity?\",\"answer\":\"Extension scores correlate with nodule size, vascular invasion, and oncocytic morphology, while intensity is associated with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology.\"}]","The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms | PDF",1789976561,38]