{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:26:40Z","timestamp":1789244800788,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T00:00:00Z","timestamp":1543708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Pleomorphic adenoma gene 1 (<jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic>) rearrangement is well known in pleomorphic adenoma (<jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>), which is histologically characterised by admixed epithelial and mesenchymal components. Multiple fusion variants of <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2<\/jats:italic> have been reported; currently, however, little is known regarding the clinicopathological impacts of these fusion types<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We examined the <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1\u2010<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2\u2010<\/jats:italic>related fusion status in 105 <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>s and 11 cases of carcinoma ex <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">CXPA<\/jats:styled-content>) arising from salivary glands and lacrimal glands to elucidate their correlation to the clinicopathological factors. Forty cases harboured <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusion genes: <jats:italic><jats:styled-content style=\"fixed-case\">CTNNB<\/jats:styled-content>1\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> in 22 cases, <jats:italic><jats:styled-content style=\"fixed-case\">CHCHD<\/jats:styled-content>7\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> in 14 cases and <jats:italic><jats:styled-content style=\"fixed-case\">LIFR<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> in four cases. Only two cases possessed <jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2<\/jats:italic> fusion genes. The mean age of <jats:italic><jats:styled-content style=\"fixed-case\">LIFR<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic>\u2010positive cases was significantly higher than that of <jats:italic><jats:styled-content style=\"fixed-case\">CTNNB<\/jats:styled-content>1\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic>\u2010 and <jats:italic><jats:styled-content style=\"fixed-case\">CHCHD<\/jats:styled-content>7\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic>\u2010positive cases (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0358). <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>s located in the submandibular gland demonstrated <jats:italic><jats:styled-content style=\"fixed-case\">CTNNB<\/jats:styled-content>1\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusion at a significantly higher rate than other fusions (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0109). Histologically, <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusion\u2010positive cases exhibited chondroid formation and plasmacytoid features more commonly (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.043, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.015, respectively) and myxoid abundant feature less frequently (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.031) than <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusion\u2010negative cases. For <jats:styled-content style=\"fixed-case\">CXPA<\/jats:styled-content>s, four <jats:italic><jats:styled-content style=\"fixed-case\">CTNNB<\/jats:styled-content>1\u2013<jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusions were detected in two salivary duct carcinomas and two myoepithelial carcinomas. Ductal formation was observed frequently (90.9%) in residual <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The presence of <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusion was associated with specific histological features in <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>. Detecting the <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> fusion gene and searching residual ductal formation in salivary gland malignant tumours with extensive hyalinisation could be useful for diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13759","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T11:46:43Z","timestamp":1539258403000},"page":"514-525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Clinicopathological effect of <i>PLAG1<\/i> fusion genes in pleomorphic adenoma and carcinoma ex pleomorphic adenoma with special emphasis on histological features"],"prefix":"10.1111","volume":"74","author":[{"given":"Miki","family":"Asahina","sequence":"first","affiliation":[{"name":"Department of Human Pathology School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-8440","authenticated-orcid":false,"given":"Tsuyoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Human Pathology School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-9370","authenticated-orcid":false,"given":"Takuo","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Human Pathology School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Fukumura","sequence":"additional","affiliation":[{"name":"Department of Human Pathology School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Mitani","sequence":"additional","affiliation":[{"name":"Department of Human Pathology School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Human Pathology School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,2]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"WHO classification of head and neck tumours","author":"el\u2010Naggar AK","year":"2017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711460106"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/hp.2000.6716"},{"key":"e_1_2_7_5_1","first-page":"182","volume-title":"Diseases of the salivary glands: pathology, diagnosis, treatment, facial nerve surgery","author":"Seifert G","year":"1986"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(93)90054-P"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(96)00204-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(90)90042-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-170"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20346"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201660"},{"key":"e_1_2_7_12_1","first-page":"918","article-title":"Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene","volume":"59","author":"Astr\u00f6m AK","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_13_1","first-page":"13","article-title":"Expression of reciprocal hybrid transcripts of HMGIC and FHIT in a pleomorphic adenoma of the parotid gland","volume":"57","author":"Geurts JM","year":"1997","journal-title":"Cancer Res."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20619"},{"key":"e_1_2_7_15_1","first-page":"1107","article-title":"Evidence of involvement of the PLAG1 gene in lipoblastomas","volume":"16","author":"Astr\u00f6m A","year":"2000","journal-title":"Int. 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