{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:32:44Z","timestamp":1787884364387,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Recently, <jats:italic>YAP1<\/jats:italic> fusion genes have been demonstrated in eccrine poroma and porocarcinoma, and the diagnostic use of YAP1 immunohistochemistry has been highlighted in this setting. In other organs,\u00a0loss of <jats:italic>YAP1<\/jats:italic> expression can reflect <jats:italic>YAP1<\/jats:italic> rearrangement or transcriptional repression, notably through <jats:italic>RB1<\/jats:italic> inactivation. In this context, our objective was to re\u2010evaluate the performance of YAP1 immunohistochemistry for the diagnosis of poroma and porocarcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The expression of the C\u2010terminal part of the YAP1 protein was evaluated by immunohistochemistry in 543 cutaneous epithelial tumours, including 27 poromas, 14 porocarcinomas and 502 other cutaneous tumours. Tumours that showed a lack of expression of YAP1 were further investigated for Rb by immunohistochemistry and for fusion transcripts by real\u2010time PCR (<jats:italic>YAP1<\/jats:italic>::<jats:italic>MAML2<\/jats:italic> and <jats:italic>YAP1<\/jats:italic>::<jats:italic>NUTM1<\/jats:italic>). The absence of YAP1 expression was observed in 24 cases of poroma (89%), 10 porocarcinoma (72%), 162 Merkel cell carcinoma (98%), 14 squamous cell carcinoma (SCC) (15%), one trichoblastoma and one sebaceoma. Fusions of <jats:italic>YAP1<\/jats:italic> were detected in only 16 cases of poroma (<jats:italic>n<\/jats:italic>\u00a0=\u00a066%), 10 porocarcinoma (71%) all lacking YAP1 expression, and in one sebaceoma. The loss of Rb expression was detected in all cases except one of YAP1\u2010deficient SCC (<jats:italic>n<\/jats:italic>\u00a0=\u00a014), such tumours showing significant morphological overlap with porocarcinoma. <jats:italic>In\u2010vitro<\/jats:italic> experiments in HaCat cells showed that <jats:italic>RB1<\/jats:italic> knockdown resulted in repression of YAP1 protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In addition to gene fusion, we report that transcriptional repression of <jats:italic>YAP1<\/jats:italic> can be observed in skin tumours with <jats:italic>RB1<\/jats:italic> inactivation, including MCC and a subset of SCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14874","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T04:05:49Z","timestamp":1675224349000},"page":"885-898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Distinct regulations driving <scp>YAP1<\/scp> expression loss in poroma, porocarcinoma and <i>RB1<\/i>\u2010deficient skin carcinoma"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2201-6914","authenticated-orcid":false,"given":"Thibault","family":"Kervarrec","sequence":"first","affiliation":[{"name":"CARADERM, French Network of Rare Cutaneous Cancer  Lille France"},{"name":"Department of Pathology University Hospital of Tours  Tours France"},{"name":"\u2018Biologie des Infections \u00e0 Polyomavirus\u2019 Team, UMR1282 INRAE University of Tours  Tours 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of Tours  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-950X","authenticated-orcid":false,"given":"Daniel","family":"Pissaloux","sequence":"additional","affiliation":[{"name":"Department of Biopathology Center L\u00e9on B\u00e9rard  Lyon France"},{"name":"University of Lyon, Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre L\u00e9on B\u00e9rard, Cancer Research Center of Lyon, Equipe Labellis\u00e9e Ligue contre le Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Tirode","sequence":"additional","affiliation":[{"name":"Department of Biopathology Center L\u00e9on B\u00e9rard  Lyon France"},{"name":"University of Lyon, Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre L\u00e9on B\u00e9rard, Cancer Research Center of Lyon, Equipe Labellis\u00e9e Ligue contre le Cancer  Lyon 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