{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T16:45:37Z","timestamp":1755794737036,"version":"3.44.0"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"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":["Int J Dermatology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) represent clinicopathological variants of a spectrum. It is known that AFX and PDS tumors harbor frequent NOTCH1\/2 mutations. However, the expression of Notch signaling pathway\u2010associated proteins in both tumor cells has not been studied before.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an immunohistochemical study by performing NOTCH1, NOTCH2, NICD, and HES1 staining on the most representative formalin\u2010fixed paraffin\u2010embedded (FFPE) tumor tissues out of sixty\u2010two patients with the first diagnosis of either AFX (<jats:italic>n<\/jats:italic>\u2009=\u200933) or PDS (<jats:italic>n<\/jats:italic>\u2009=\u200929) in a single tertiary medical center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten patients (PDS, <jats:italic>n<\/jats:italic>\u2009=\u20099; AFX, <jats:italic>n<\/jats:italic>\u2009=\u20091) had disease progression in terms of locoregional relapse, including local recurrence and regional lymph node metastasis, with a median time\u2010to\u2010(first)\u2010recurrence interval of 8\u2009months after a wide local excision. Among all the Notch expression profiles, only the upregulated NOTCH2 expression has a positive correlation with disease progression [odds ratio (OR): 1.02, 95% confidence interval (CI): 1\u20131.04, <jats:italic>p<\/jats:italic>\u2009=\u20090.029]. Furthermore, HES1 is activated through the NOTCH2 signaling pathway (<jats:italic>r<\/jats:italic> (60)\u2009=\u20090.27, <jats:italic>p<\/jats:italic>\u2009=\u20090.032) rather than NOTCH1, and NOTCH1 does not appear to be functionally active.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Upregulated NOTCH2 expression plays a significant role in disease progression, in part through the canonical signaling pathway involving the downstream effector HES1. Targeting NOTCH2 signaling might hold therapeutic promise in patients with disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijd.17844","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T09:50:36Z","timestamp":1747648236000},"page":"1416-1424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Upregulated NOTCH2 Expression Is Implicated in the Clinical Aggressiveness of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-6176","authenticated-orcid":false,"given":"Yi\u2010Pei","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology St. Josef Hospital, Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahimeh","family":"Razegphpour","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology St. Josef Hospital, Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Sorescu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology St. Josef Hospital, Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"St\u00fccker","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology St. Josef Hospital, Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thilo","family":"Gambichler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology St. Josef Hospital, Ruhr\u2010University Bochum  Bochum Germany"},{"name":"Department of Dermatology, Dortmund Hospital gGmbH University Witten\/Herdecke  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19850101)55:1<172::AID-CNCR2820550127>3.0.CO;2-F"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31825359e1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.168"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.146"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02168-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010009\u20100305\u20102"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2006.04.003"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-0899-4_14"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8859-4"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00934-y"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01439-z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.045"},{"volume-title":"World Health Organization Classification of Tumours. 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