{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:49:52Z","timestamp":1777592992838,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,10,19]],"date-time":"2017-10-19T00:00:00Z","timestamp":1508371200000},"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":[[2018,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Multiple genetic alterations, including alternative lengthening of telomeres (<jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>) and<jats:italic><jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content><\/jats:italic>mutations, have been described in angiosarcoma. Loss of \u03b1\u2010thalassaemia\/mental retardation syndrome X\u2010linked (<jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>) and death domain\u2010associated protein 6 (<jats:styled-content style=\"fixed-case\">DAXX<\/jats:styled-content>) expression is frequently associated with the<jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>phenotype. Additionally, inhibition of<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>signalling induces the development of malignant vascular tumours in mice, indicating a tumour suppressive role of the<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>pathway in the pathogenesis of angiosarcoma. The aim of this study was to evaluate the immunohistochemical expression of<jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">DAXX<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>receptors (<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>2) in a large cohort of angiosarcomas, and study their clinicopathological and prognostic significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>One hundred and forty cases of angiosarcoma were stained for<jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">DAXX<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>2.<jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>loss (&lt;10% labelling) was seen in seven of 118 (6%) cases, and was more frequent in deep soft tissue tumours than in other body sites (<jats:italic>P<\/jats:italic>= 0.004). Angiosarcomas with<jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>loss were associated with worse event\u2010free survival than angiosarcomas with retained<jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>expression (<jats:italic>P<\/jats:italic>= 0.003).<jats:styled-content style=\"fixed-case\">DAXX<\/jats:styled-content>was retained in all specimens examined. Decreased<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1 expression (\u22641+ intensity) was seen in 29 of 123 (24%) cases, and was associated with a cutaneous site of origin (<jats:italic>P<\/jats:italic>= 0.013) and advanced disease (<jats:italic>P<\/jats:italic>= 0.026).<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>2 expression was decreased in 16 of 103 (16%) cases, was associated with visceral tumours (<jats:italic>P<\/jats:italic>= 0.001), and correlated with worse disease\u2010specific survival (<jats:italic>P<\/jats:italic>= 0.033).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">ATRX<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>2 expression varies in angiosarcomas and shows significant correlations with site of origin and poor clinical outcome, thus highlighting the biological heterogeneity within this tumour type.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13337","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T10:04:37Z","timestamp":1502359477000},"page":"239-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinicopathological analysis of<scp>ATRX<\/scp>,<scp>DAXX<\/scp>and<scp>NOTCH<\/scp>receptor expression in angiosarcomas"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3490","authenticated-orcid":false,"given":"Gauri","family":"Panse","sequence":"first","affiliation":[{"name":"Department of Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-0923","authenticated-orcid":false,"given":"John SA","family":"Chrisinger","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheuk H","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davis R","family":"Ingram","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samia","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalida","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-7007","authenticated-orcid":false,"given":"Heather","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas MD Anderson Cancer Center Houston TX USA"},{"name":"Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Lien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas MD Anderson Cancer Center Houston TX USA"},{"name":"Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,19]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Enzinger and Weiss's soft tissue tumors","author":"Goldblum 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