Investigation of the RB1-SOX2 axis constitutes a tool for viral status determination and diagnosis in Merkel cell carcinoma - Archive ouverte HAL Access content directly
Journal Articles Virchows Archiv Year : 2022

Investigation of the RB1-SOX2 axis constitutes a tool for viral status determination and diagnosis in Merkel cell carcinoma

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Soumanth Thanguturi
Anne Tallet
  • Function : Author
  • PersonId : 956871
Elodie Miquelestorena-Standley
  • Function : Author
  • PersonId : 1004554
Charlée Nardin
Francois Aubin
  • Function : Author
  • PersonId : 1101823
Roland Houben
  • Function : Author
  • PersonId : 1084028
David Schrama
Gaëlle Fromont
Marie-Laure Jullie
Nicolas Macagno
Pauline Gaboriaud
  • Function : Author
  • PersonId : 1092341
Patricia Berthon
Antoine Touzé
  • Function : Author
  • PersonId : 1151889
Serge Guyétant
Mahtab Samimi

Abstract

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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hal-03737771 , version 1 (25-07-2022)

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Soumanth Thanguturi, Anne Tallet, Elodie Miquelestorena-Standley, Catherine Coco, Yannick Le Corre, et al.. Investigation of the RB1-SOX2 axis constitutes a tool for viral status determination and diagnosis in Merkel cell carcinoma. Virchows Archiv, 2022, 480 (6), pp.1239-1254. ⟨10.1007/s00428-022-03315-6⟩. ⟨hal-03737771⟩
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