{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:57:50Z","timestamp":1747184270759,"version":"3.40.5"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cutaneous squamous cell carcinoma (cSCC) incidence continues to increase globally with, as of yet, an unmet need for reliable prognostic biomarkers to identify patients at increased risk of metastasis. The aim of the present study was to test the prognostic potential of the combined immunohistochemical expression of the autophagy regulatory biomarkers, AMBRA1 and SQSTM1, to identify high\u2010risk patient subsets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective cohort of 68 formalin\u2010fixed paraffin\u2010embedded primary cSCCs with known 5\u2010year metastatic outcomes were subjected to automated immunohistochemical staining for AMBRA1 and SQSTM1. Digital images of stained slides were annotated to define four regions of interest: the normal and peritumoral epidermis, the tumor mass, and the tumor growth front. H\u2010score analysis was used to semi\u2010quantify AMBRA1 or SQSTM1 expression in each region of interest using Aperio ImageScope software, with receiver operator characteristics and Kaplan\u2013Meier analysis used to assess prognostic potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combined loss of expression of AMBRA1 in the tumor growth front and SQSTM1 in the peritumoral epidermis identified patients with poorly differentiated cSCCs at risk of metastasis (*<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, these proof of concept data suggest loss of the combined expression of AMBRA1 in the cSCC growth front and SQSTM1 in the peritumoral epidermis as a putative prognostic biomarker for poorly differentiated cSCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.14590","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T13:44:51Z","timestamp":1709214291000},"page":"450-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The combined immunohistochemical expression of AMBRA1 and SQSTM1 identifies patients with poorly differentiated cutaneous squamous cell carcinoma at risk of metastasis: A proof of concept study"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7196-4101","authenticated-orcid":false,"given":"Michael H.","family":"Alexander","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University  Newcastle upon Tyne UK"},{"name":"AMLo Biosciences, Newcastle Helix, Newcastle upon Tyne  Newcastle upon Tyne UK"},{"name":"Department of Dermatology and Cutaneous Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Cousins","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University  Newcastle upon Tyne UK"},{"name":"AMLo Biosciences, Newcastle Helix, Newcastle upon Tyne  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-9614","authenticated-orcid":false,"given":"Tom","family":"Ewen","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University  Newcastle upon Tyne UK"},{"name":"AMLo Biosciences, Newcastle Helix, Newcastle upon Tyne  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew P.","family":"South","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penny","family":"Lovat","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University  Newcastle upon Tyne UK"},{"name":"AMLo Biosciences, Newcastle Helix, Newcastle upon Tyne  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niki","family":"Stefanos","sequence":"additional","affiliation":[{"name":"Cellular Pathology, Addenbrookes Hospital  Cambridge 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