{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:30:17Z","timestamp":1760243417419,"version":"3.44.0"},"reference-count":34,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["Junior Clinical Investigator Award"],"award-info":[{"award-number":["Junior Clinical Investigator Award"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003514","name":"Kommunfullm\u00e4ktige, Stockholms Stad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Swedish Society for Medical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2021,4,28]]},"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Upregulation of the <jats:italic>telomerase reverse transcriptase<\/jats:italic> (<jats:italic>TERT<\/jats:italic>) gene is a frequent finding in follicular thyroid carcinomas (FTCs) with metastatic features. The augmented expression is usually caused by <jats:italic>TERT<\/jats:italic> promoter mutations. As TERT protein immunohistochemistry might not correlate to <jats:italic>TERT<\/jats:italic> mRNA levels in follicular thyroid tumours, we therefore sought to determine if visualisation of <jats:italic>TERT<\/jats:italic> mRNA through in situ hybridisation could highlight high-risk cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We collected formalin-fixated paraffin-embedded tissues from 26 follicular thyroid tumours; 7 FTCs, 2 follicular thyroid tumours of uncertain malignant potential (FT-UMPs) and a single H\u00fcrthle cell carcinoma with established <jats:italic>TERT<\/jats:italic> promoter mutations and gene expression, as well as 16 FTCs with no <jats:italic>TERT<\/jats:italic> gene aberrancy or gene expression, and assessed them using RNA Scope in situ hybridisation (ISH) and <jats:italic>TERT<\/jats:italic> probes targeting the two main <jats:italic>TERT<\/jats:italic> transcripts (<jats:italic>TERT1 and TERT2<\/jats:italic>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                     <jats:italic>TERT 1<\/jats:italic> and\/or <jats:italic>2<\/jats:italic> mRNA was found by ISH in 8\/10 cases with established promoter mutations and mRNA expression, whereas all 16 cases without <jats:italic>TERT<\/jats:italic> gene aberrancies or gene expression were negative (Fisher\u2019s exact p&lt;0.001). Strikingly, <jats:italic>TERT<\/jats:italic> mRNA was visualised in the nuclear compartment only, thereby corroborating earlier studies suggesting a non-conventional role for <jats:italic>TERT<\/jats:italic> in tumour biology. Moreover, <jats:italic>TERT<\/jats:italic> mRNA expression was scattered across the tissue sections and only found in a few percentages of tumour nuclei.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                     <jats:italic>TERT<\/jats:italic> mRNA seems to be focally expressed and localised exclusively to the nucleus in <jats:italic>TERT<\/jats:italic> promoter mutated follicular thyroid tumours, possibly reflecting a true biological and unorthodox phenomenon worthy of further investigations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2021-207631","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T13:28:15Z","timestamp":1621430895000},"page":"658-662","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Nuclear-specific accumulation of <i>telomerase reverse transcriptase<\/i> (<i>TERT<\/i>) mRNA in <i>TERT<\/i> promoter mutated follicular thyroid tumours visualised by in situ hybridisation: a possible clinical screening tool?"],"prefix":"10.1136","volume":"75","author":[{"given":"L Samuel","family":"Hellgren","sequence":"first","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Kaufeldt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan O","family":"Paulsson","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hysek","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Stenman","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Zedenius","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"H\u00f6\u00f6g","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5945-9081","authenticated-orcid":false,"given":"C Christofer","family":"Juhlin","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"2025092506304989000_75.10.658.1","unstructured":"American Joint Committee on Cancer, American Cancer Society editors Amin MB . 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