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Investigation of the RB1-SOX2 axis constitutes a tool for viral status determination and diagnosis in Merkel cell carcinoma.
Thanguturi, Soumanth; Tallet, Anne; Miquelestorena-Standley, Elodie; Coco, Catherine; Le Corre, Yannick; Hainaut-Wierzbicka, Ewa; Blom, Astrid; Saiag, Philippe; Beneton, Nathalie; Bens, Guido; Zaragoza, Julia; Nardin, Charlee; Aubin, François; Dinulescu, Monica; Machet, Marie-Christine; Houben, Roland; Schrama, David; Collin, Christine; Fromont, Gaëlle; Jullie, Marie-Laure; Macagno, Nicolas; Gaboriaud, Pauline; Berthon, Patricia; Touzé, Antoine; Guyétant, Serge; Samimi, Mahtab; Kervarrec, Thibault.
Afiliação
  • Thanguturi S; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Tallet A; Platform of Somatic Tumor Molecular Genetics, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Miquelestorena-Standley E; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Coco C; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Le Corre Y; Dermatology Department, LUNAM Université, CHU Angers, Angers, France.
  • Hainaut-Wierzbicka E; Dermatology Department, Université de Poitiers, CHU de Poitiers, 2 rue de la Milétrie, Poitiers, France.
  • Blom A; Department of General and Oncologic Dermatology, APHP & Research unit EA 4340, CARADERM network Ambroise-Paré hospital, Paris-Saclay University, university of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt, France.
  • Saiag P; Department of General and Oncologic Dermatology, APHP & Research unit EA 4340, CARADERM network Ambroise-Paré hospital, Paris-Saclay University, university of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt, France.
  • Beneton N; Dermatology Department, CHR Le Mans, 194 avenue Rubillard, Le Mans Cedex 09, France.
  • Bens G; Dermatology Department, CHR d'Orléans, 14 avenue de l'hôpital, Orléans, France.
  • Zaragoza J; Dermatology Department, CHR d'Orléans, 14 avenue de l'hôpital, Orléans, France.
  • Nardin C; Dermatology Department, Université de Franche Comté, CHU Besançon, 2 boulevard Fleming, EA3181, IFR133, Besançon, France.
  • Aubin F; Dermatology Department, Université de Franche Comté, CHU Besançon, 2 boulevard Fleming, EA3181, IFR133, Besançon, France.
  • Dinulescu M; Dermatology Department, CHR Rennes, Cedex,;InstitutDermatologique du Grand Ouest (IDGO), 2 rue Henri le Guilloux, Rennes , France.
  • Machet MC; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Houben R; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
  • Schrama D; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
  • Collin C; Platform of Somatic Tumor Molecular Genetics, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Fromont G; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Jullie ML; Department of Pathology, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Tours, France.
  • Macagno N; Department of Pathology, APHM, Timone University Hospital, Marseille, France.
  • Gaboriaud P; Biologie des infections à polyomavirus" team, UMR INRA ISP 1282, Université de Tours, Tours, France.
  • Berthon P; Biologie des infections à polyomavirus" team, UMR INRA ISP 1282, Université de Tours, Tours, France.
  • Touzé A; Biologie des infections à polyomavirus" team, UMR INRA ISP 1282, Université de Tours, Tours, France.
  • Guyétant S; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
  • Samimi M; Biologie des infections à polyomavirus" team, UMR INRA ISP 1282, Université de Tours, Tours, France.
  • Kervarrec T; Biologie des infections à polyomavirus" team, UMR INRA ISP 1282, Université de Tours, Tours, France.
Virchows Arch ; 480(6): 1239-1254, 2022 Jun.
Article em En | MEDLINE | ID: mdl-35412101
MCC (Merkel cell carcinoma) is an aggressive neuroendocrine cutaneous neoplasm. Integration of the Merkel cell polyomavirus (MCPyV) is observed in about 80% of the cases, while the remaining 20% are related to UV exposure. Both MCPyV-positive and -negative MCCs-albeit by different mechanisms-are associated with RB1 inactivation leading to overexpression of SOX2, a major contributor to MCC biology. Moreover, although controversial, loss of RB1 expression seems to be restricted to MCPyV-negative cases.The aim of the present study was to assess the performances of RB1 loss and SOX2 expression detected by immunohistochemistry to determine MCPyV status and to diagnose MCC, respectively.Overall, 196 MCC tumors, 233 non-neuroendocrine skin neoplasms and 70 extra-cutaneous neuroendocrine carcinomas (NEC) were included. SOX2 and RB1 expressions were assessed by immunohistochemistry in a tissue micro-array. Diagnostic performances were determined using the likelihood ratio (LHR).RB1 expression loss was evidenced in 27% of the MCC cases, 12% of non-neuroendocrine skin tumors and 63% of extra-cutaneous NEC. Importantly, among MCC cases, RB1 loss was detected in all MCPyV(-) MCCs, while MCPyV( +) cases were consistently RB1-positive (p < 0.001). SOX2 diffuse expression was observed in 92% of the MCC cases and almost never observed in non-neuroendocrine skin epithelial neoplasms (2%, p < 0.0001, LHR + = 59). Furthermore, SOX2 diffuse staining was more frequently observed in MCCs than in extra-cutaneous NECs (30%, p < 0.001, LHR + = 3.1).These results confirm RB1 as a robust predictor of MCC viral status and further suggest SOX2 to be a relevant diagnostic marker of MCC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Infecções Tumorais por Vírus / Carcinoma de Célula de Merkel / Infecções por Polyomavirus / Poliomavírus das Células de Merkel Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Virchows Arch Assunto da revista: BIOLOGIA MOLECULAR / PATOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: França País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Infecções Tumorais por Vírus / Carcinoma de Célula de Merkel / Infecções por Polyomavirus / Poliomavírus das Células de Merkel Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Virchows Arch Assunto da revista: BIOLOGIA MOLECULAR / PATOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: França País de publicação: Alemanha