{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:31:22Z","timestamp":1780320682219,"version":"3.54.1"},"reference-count":78,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dystrophic Epidermolysis Bullosa Research Association (DEBRA) France","award":["RS20\/75-59"],"award-info":[{"award-number":["RS20\/75-59"]}]},{"DOI":"10.13039\/501100004099","name":"Ligue contre le Cancer","doi-asserted-by":"publisher","award":["RS20\/75-59"],"award-info":[{"award-number":["RS20\/75-59"]}],"id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Soci\u00e9t\u00e9 Fran\u00e7aise de Dermatologie, and EB Research Partnership (EBRP)","award":["RS20\/75-59"],"award-info":[{"award-number":["RS20\/75-59"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.<\/jats:p>","DOI":"10.3390\/cancers16132476","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T07:57:45Z","timestamp":1720425465000},"page":"2476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-4256","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Ragot","sequence":"first","affiliation":[{"name":"Laboratory of Genetic Skin Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1163, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Gaucher","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1163, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Bonnet des Claustres","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1163, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Basset","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1163, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Boudan","sequence":"additional","affiliation":[{"name":"Reference Center for Genodermatoses (\u201cMaladies G\u00e9n\u00e9tiques \u00e0 Expression Cutan\u00e9e\u201d, MAGEC), Saint-Louis Hospital (Assistance Publique\u2014H\u00f4pitaux de Paris), 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Battistella","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saint-Louis Hospital (Assistance Publique\u2014H\u00f4pitaux de Paris), Universit\u00e9 Paris Cit\u00e9, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Bourrat","sequence":"additional","affiliation":[{"name":"Reference Center for Genodermatoses (\u201cMaladies G\u00e9n\u00e9tiques \u00e0 Expression Cutan\u00e9e\u201d, MAGEC), Saint-Louis Hospital (Assistance Publique\u2014H\u00f4pitaux de Paris), 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Hovnanian","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1163, 75015 Paris, France"},{"name":"Department of Genomic Medicine of Rare Diseases, Necker Hospital for Sick Children (Assistance Publique\u2014H\u00f4pitaux de Paris), Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-2769","authenticated-orcid":false,"given":"Matthias","family":"Titeux","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1163, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/ng1193-287","article-title":"A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in Hallopeau-Siemens dystrophic epidermolysis bullosa","volume":"5","author":"Hilal","year":"1993","journal-title":"Nat. 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