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

被引:0
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作者
Ragot, Helene [1 ]
Gaucher, Sonia [1 ]
Bonnet des Claustres, Mathilde [1 ]
Basset, Justine [1 ]
Boudan, Rose [2 ]
Battistella, Maxime [3 ]
Bourrat, Emmanuelle [2 ]
Hovnanian, Alain [1 ,4 ]
Titeux, Matthias [1 ]
机构
[1] Univ Paris Cite, Imagine Inst, Lab Genet Skin Dis, INSERM UMR 1163, F-75015 Paris, France
[2] St Louis Hosp, Assistance Publ Hop Paris, Reference Ctr Genodermatoses Malad Genet Express C, MAGEC, F-75010 Paris, France
[3] Univ Paris Cite, St Louis Hosp, Assistance Publ Hop Paris, Dept Pathol, F-75010 Paris, France
[4] Univ Paris Cite, Necker Hosp Sick Children, Assistance Publ Hop Paris, Dept Genom Med Rare Dis, F-75015 Paris, France
关键词
recessive dystrophic epidermolysis bullosa; cutaneous squamous cell carcinoma; citrullinated histone H3; CIRCULATING TUMOR-CELLS; METASTASIS; PROGRESSION; IMMUNITY; PROMOTE; RISK; COLONIZATION; INFLAMMATION; EXPRESSION; EXPERIENCE;
D O I
10.3390/cancers16132476
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe hereditary skin disease characterized by skin and mucosa fragility. RDEB patients are predisposed to the development of life-threatening cutaneous squamous cell carcinoma (SCC). In this study, we investigated the immune profiles of SCCs occurring in a cohort of RDEB patients and compared them with clinical, histopathological and prognostic features. We describe two distinct clinical outcomes in RDEB patients with cutaneous SCCs. A majority of RDEB patients had local and not rapidly life-threatening SCC, while others developed early aggressive and metastatic SCCs. The high-risk primary RDEB-SCC was associated with a tumor microenvironment displaying a higher neutrophil-to-lymphocyte infiltration ratio. Increased levels of citrullinated histone H3, a marker of neutrophil extracellular traps (NET), were detected in tumoral skin and in the serum of RDEB patients with high-risk primary SCC.Abstract 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.
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页数:17
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