PMID- 35412101 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20220614 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 480 IP - 6 DP - 2022 Jun TI - Investigation of the RB1-SOX2 axis constitutes a tool for viral status determination and diagnosis in Merkel cell carcinoma. PG - 1239-1254 LID - 10.1007/s00428-022-03315-6 [doi] AB - 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. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Thanguturi, Soumanth AU - Thanguturi S AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Tallet, Anne AU - Tallet A AD - Platform of Somatic Tumor Molecular Genetics, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Miquelestorena-Standley, Elodie AU - Miquelestorena-Standley E AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Coco, Catherine AU - Coco C AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Le Corre, Yannick AU - Le Corre Y AD - Dermatology Department, LUNAM Universite, CHU Angers, Angers, France. FAU - Hainaut-Wierzbicka, Ewa AU - Hainaut-Wierzbicka E AD - Dermatology Department, Universite de Poitiers, CHU de Poitiers, 2 rue de la Miletrie, Poitiers, France. FAU - Blom, Astrid AU - Blom A AD - Department of General and Oncologic Dermatology, APHP & Research unit EA 4340, CARADERM network Ambroise-Pare hospital, Paris-Saclay University, university of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt, France. FAU - Saiag, Philippe AU - Saiag P AD - Department of General and Oncologic Dermatology, APHP & Research unit EA 4340, CARADERM network Ambroise-Pare hospital, Paris-Saclay University, university of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt, France. FAU - Beneton, Nathalie AU - Beneton N AD - Dermatology Department, CHR Le Mans, 194 avenue Rubillard, Le Mans Cedex 09, France. FAU - Bens, Guido AU - Bens G AD - Dermatology Department, CHR d'Orleans, 14 avenue de l'hopital, Orleans, France. FAU - Zaragoza, Julia AU - Zaragoza J AD - Dermatology Department, CHR d'Orleans, 14 avenue de l'hopital, Orleans, France. FAU - Nardin, Charlee AU - Nardin C AD - Dermatology Department, Universite de Franche Comte, CHU Besancon, 2 boulevard Fleming, EA3181, IFR133, Besancon, France. FAU - Aubin, Francois AU - Aubin F AD - Dermatology Department, Universite de Franche Comte, CHU Besancon, 2 boulevard Fleming, EA3181, IFR133, Besancon, France. FAU - Dinulescu, Monica AU - Dinulescu M AD - Dermatology Department, CHR Rennes, Cedex,;InstitutDermatologique du Grand Ouest (IDGO), 2 rue Henri le Guilloux, Rennes , France. FAU - Machet, Marie-Christine AU - Machet MC AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Houben, Roland AU - Houben R AD - Department of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany. FAU - Schrama, David AU - Schrama D AD - Department of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany. FAU - Collin, Christine AU - Collin C AD - Platform of Somatic Tumor Molecular Genetics, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Fromont, Gaelle AU - Fromont G AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Jullie, Marie-Laure AU - Jullie ML AD - Department of Pathology, Universite de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Tours, France. FAU - Macagno, Nicolas AU - Macagno N AD - Department of Pathology, APHM, Timone University Hospital, Marseille, France. FAU - Gaboriaud, Pauline AU - Gaboriaud P AD - Biologie des infections a polyomavirus" team, UMR INRA ISP 1282, Universite de Tours, Tours, France. FAU - Berthon, Patricia AU - Berthon P AD - Biologie des infections a polyomavirus" team, UMR INRA ISP 1282, Universite de Tours, Tours, France. FAU - Touze, Antoine AU - Touze A AD - Biologie des infections a polyomavirus" team, UMR INRA ISP 1282, Universite de Tours, Tours, France. FAU - Guyetant, Serge AU - Guyetant S AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. AD - Biologie des infections a polyomavirus" team, UMR INRA ISP 1282, Universite de Tours, Tours, France. FAU - Samimi, Mahtab AU - Samimi M AD - Biologie des infections a polyomavirus" team, UMR INRA ISP 1282, Universite de Tours, Tours, France. AD - Department of Dermatology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. FAU - Kervarrec, Thibault AU - Kervarrec T AUID- ORCID: 0000-0002-2201-6914 AD - Department of Pathology, Universite de Tours, Centre Hospitalier Universitaire de Tours, Tours, France. thibaultkervarrec@yahoo.fr. AD - Biologie des infections a polyomavirus" team, UMR INRA ISP 1282, Universite de Tours, Tours, France. thibaultkervarrec@yahoo.fr. LA - eng PT - Journal Article DEP - 20220412 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (RB1 protein, human) RN - 0 (Retinoblastoma Binding Proteins) RN - 0 (SOX2 protein, human) RN - 0 (SOXB1 Transcription Factors) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - *Carcinoma, Merkel Cell/diagnosis/pathology MH - Humans MH - *Merkel cell polyomavirus/metabolism MH - *Polyomavirus Infections/complications/metabolism MH - Retinoblastoma Binding Proteins MH - SOXB1 Transcription Factors/metabolism MH - *Skin Neoplasms/pathology MH - *Tumor Virus Infections/complications MH - Ubiquitin-Protein Ligases OTO - NOTNLM OT - Merkel cell carcinoma OT - Polyomavirus OT - RB1 immunohistochemistry OT - SOX2 EDAT- 2022/04/13 06:00 MHDA- 2022/06/14 06:00 CRDT- 2022/04/12 12:04 PHST- 2022/02/25 00:00 [received] PHST- 2022/03/18 00:00 [accepted] PHST- 2022/03/17 00:00 [revised] PHST- 2022/04/13 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/04/12 12:04 [entrez] AID - 10.1007/s00428-022-03315-6 [pii] AID - 10.1007/s00428-022-03315-6 [doi] PST - ppublish SO - Virchows Arch. 2022 Jun;480(6):1239-1254. doi: 10.1007/s00428-022-03315-6. Epub 2022 Apr 12.