{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:31:04Z","timestamp":1788003064674,"version":"build-2784847793"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T00:00:00Z","timestamp":1452470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004358","name":"Samsung","doi-asserted-by":"publisher","award":["CR0113031"],"award-info":[{"award-number":["CR0113031"]}],"id":[{"id":"10.13039\/100004358","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"Aim<\/jats:title>Diffuse sclerosing variant of papillary thyroid carcinoma (DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content>) is an uncommon variant of PTC<\/jats:styled-content>, and its prognostic significance remains controversial. The aim of this study was to investigate the major genetic alterations of DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content> and their prognostic implications.<\/jats:p><\/jats:sec>Methods and results<\/jats:title>We included 37 patients with DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content> who underwent thyroid surgery and had formalin\u2010fixed paraffin\u2010embedded samples. We tested for a panel of genetic alterations, including BRAF<\/jats:italic>V<\/jats:sup><\/jats:styled-content>600E<\/jats:sup>, NRAS<\/jats:styled-content><\/jats:italic> codon 61, HRAS<\/jats:styled-content><\/jats:italic> codon 12\/13\/61 and KRAS<\/jats:styled-content><\/jats:italic> codon 12\/13 point mutations as well as RET<\/jats:styled-content>\/PTC<\/jats:styled-content>1<\/jats:italic>, RET<\/jats:styled-content>\/PTC<\/jats:styled-content>3<\/jats:italic> and PAX<\/jats:styled-content>8\/PPAR<\/jats:styled-content><\/jats:italic>\u03b3 rearrangements using reverse transcription real\u2010time polymerase chain reaction (PCR<\/jats:styled-content>). All genetic alterations found on PCR<\/jats:styled-content> were confirmed by Sanger sequencing. Associations between the identified genetic alterations and clinicopathological characteristics were evaluated. Among 37 cases of DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content>, 17 were positive for RET<\/jats:styled-content>\/PTC<\/jats:styled-content>1<\/jats:italic> (46%), six for RET<\/jats:styled-content>\/PTC<\/jats:styled-content>3<\/jats:italic> (16%) and nine for BRAF<\/jats:italic>V<\/jats:sup><\/jats:styled-content>600E<\/jats:sup> (24%). All mutations\/rearrangements were mutually exclusive. The remaining five cases had none of the above genetic alterations. DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content> with RET<\/jats:styled-content>\/PTC<\/jats:styled-content>3<\/jats:italic> rearrangement was associated with advanced\u2010stage disease, including T4 and distant metastasis (P<\/jats:italic> < 0.05). Patients with RET<\/jats:styled-content>\/PTC<\/jats:styled-content>3<\/jats:italic> showed a higher frequency of persistent disease (P<\/jats:italic> < 0.01). In contrast, DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content> with RET<\/jats:styled-content>\/PTC<\/jats:styled-content>1<\/jats:italic> was associated with a higher prevalence of disease remission (P<\/jats:italic> < 0.05) and coexistent Hashimoto's thyroiditis (P<\/jats:italic> < 0.01).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Taken together, RET<\/jats:styled-content>\/PTC<\/jats:styled-content><\/jats:italic> rearrangement was the major genetic alteration seen in patients with DSV<\/jats:styled-content>\u2010PTC<\/jats:styled-content>, and the RET<\/jats:styled-content>\/PTC<\/jats:styled-content>3<\/jats:italic> rearrangement was associated with advanced stage at diagnosis and poor clinical outcome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12902","type":"journal-article","created":{"date-parts":[[2015,11,14]],"date-time":"2015-11-14T15:02:43Z","timestamp":1447513363000},"page":"45-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Diffuse sclerosing variant of papillary thyroid carcinoma: major genetic alterations and prognostic implications"],"prefix":"10.1111","volume":"69","author":[{"given":"Ji Y","family":"Joung","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine Thyroid Center Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-2437","authenticated-orcid":false,"given":"Tae H","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine Thyroid Center Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae J","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine Thyroid Center Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Mi","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine Thyroid Center Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Y","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine Thyroid Center Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye W","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Social and Preventive Medicine Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Y","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pathology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young L","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pathology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun S","family":"Yim","sequence":"additional","affiliation":[{"name":"BioSewoom Inc. 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