{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:14:29Z","timestamp":1790252069526,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T00:00:00Z","timestamp":1599955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007278","name":"Henry Ford Health System","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007278","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the molecular underpinnings of the rare aggressive prostate cancer variants adenosquamous carcinoma, pleomorphic giant\u2010cell carcinoma, and sarcomatoid carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We retrieved 19 tumours with one or more variant(s), and performed ERG immunohistochemistry, a next\u2010generation sequencing assay targeting recurrent gene fusions, and fluorescence<jats:italic>in\u2010situ<\/jats:italic>hybridisation (FISH) for<jats:italic>ERG<\/jats:italic>and<jats:italic>BRAF<\/jats:italic>. Divergent differentiation included: sarcomatoid carcinoma (<jats:italic>n<\/jats:italic>\u00a0=\u00a010), adenosquamous carcinoma (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), and pleomorphic giant\u2010cell carcinoma (<jats:italic>n<\/jats:italic>\u00a0=\u00a07). Five patients had more than one variant. Four had variants only in metastases.<jats:italic>ERG<\/jats:italic>rearrangement was detected in nine (47%, seven via sequencing, showing<jats:italic>TMPRSS2<\/jats:italic>\u2013<jats:italic>ERG<\/jats:italic>fusions and one<jats:italic>GRHL2<\/jats:italic>\u2013<jats:italic>ERG<\/jats:italic>fusion, and two via FISH, showing rearrangement via deletion). ERG was immunohistochemically positive in the adenocarcinoma in eight of nine (89%) patients, but was immunohistochemically positive in the variant in only five of nine patients (56%, typically decreased). One patient had a false\u2010positive ERG immunohistochemical result in the sarcomatoid component despite a negative FISH result. Two (11%) harboured<jats:italic>BRAF<\/jats:italic>fusions (<jats:italic>FAM131A<\/jats:italic>\u2013<jats:italic>BRAF<\/jats:italic>and<jats:italic>SND1<\/jats:italic>\u2013<jats:italic>BRAF<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>ERG<\/jats:italic>fusions are present in these rare prostate cancer variants with a frequency close to that in conventional prostate cancer (9\/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma, but is less sensitive for the variant histology, with weak to negative staining. Adenosquamous and sarcomatoid variants can, particularly, occur together. Molecular assessment may be an additional tool in selected cases to confirm the prostatic origin of unusual tumours. The presence of two<jats:italic>BRAF<\/jats:italic>rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1\u20132% of prostate cancers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14205","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T15:00:30Z","timestamp":1594220430000},"page":"890-899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Gene fusion characterisation of rare aggressive prostate cancer variants\u2014adenosquamous carcinoma, pleomorphic giant\u2010cell carcinoma, and sarcomatoid carcinoma: an analysis of 19 cases"],"prefix":"10.1111","volume":"77","author":[{"given":"Mohamed","family":"Alhamar","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Tudor Vladislav","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-4607","authenticated-orcid":false,"given":"Steven C","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology Virginia Commonwealth University Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial University St John\u2019s Newfoundland Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A","family":"Favazza","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M","family":"Alani","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M","family":"Ittmann","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole D","family":"Riddle","sequence":"additional","affiliation":[{"name":"Department of Pathology USF Health Ruffolo, Hooper, and Associates Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J","family":"Whiteley","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh S","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Carskadon","sequence":"additional","affiliation":[{"name":"Department of Urology Vattikutti Urology Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C","family":"Gomez\u2010Gelvez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjay A","family":"Chitale","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"},{"name":"Department of Pathology Wayne State University School of Medicine Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-9772","authenticated-orcid":false,"given":"Nallasivam","family":"Palanisamy","sequence":"additional","affiliation":[{"name":"Department of Urology Vattikutti Urology Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Hes","sequence":"additional","affiliation":[{"name":"Department of Pathology Charles University Faculty of Medicine Plzen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-8846","authenticated-orcid":false,"given":"Kiril","family":"Trpkov","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cumming School of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-1460","authenticated-orcid":false,"given":"Sean R","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute Henry Ford Health System Detroit MI USA"},{"name":"Department of Pathology Wayne State University School of Medicine Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.08074.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800052"},{"key":"e_1_2_10_4_1","first-page":"170","volume-title":"World Health Organization classification of tumours of the urinary system and male genital organs","author":"Epstein JI","year":"2016"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12493"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2019.11.020"},{"issue":"423","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"423.e5","DOI":"10.1016\/j.urology.2005.08.013","article-title":"Clonality of sarcomatous and carcinomatous elements in sarcomatoid carcinoma of the prostate","volume":"67","author":"Ray ME","year":"2006","journal-title":"Urology"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13806"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.234"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2166"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13526"},{"key":"e_1_2_10_12_1","unstructured":"KimP FusionGDBZX.Fusion Gene annotation DataBase. 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