Distinct regulations driving YAP1 expression loss in poroma, porocarcinoma and RB1-deficient skin carcinoma.

Autor: Kervarrec T; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, University Hospital of Tours, Tours, France.; 'Biologie des Infections à Polyomavirus' Team, UMR1282 INRAE, University of Tours, Tours, France., Frouin E; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, University Hospital of Poitiers, University of Poitiers, LITEC, Poitiers, France., Collin C; Platform of Solid Tumor Molecular Genetics, University Hospital Center of Tours, Tours, France., Tallet A; Platform of Solid Tumor Molecular Genetics, University Hospital Center of Tours, Tours, France., Tallegas M; Platform of Solid Tumor Molecular Genetics, University Hospital Center of Tours, Tours, France., Pissaloux D; Department of Biopathology, Center Léon Bérard, Lyon, France.; University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France., Tirode F; Department of Biopathology, Center Léon Bérard, Lyon, France.; University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France., Guyétant S; Department of Pathology, University Hospital of Tours, Tours, France.; 'Biologie des Infections à Polyomavirus' Team, UMR1282 INRAE, University of Tours, Tours, France.; Department of Pathology, University Hospital of Poitiers, University of Poitiers, LITEC, Poitiers, France., Samimi M; Department of Dermatology, University Hospital Center of Tours, Tours, France., Gaboriaud P; 'Biologie des Infections à Polyomavirus' Team, UMR1282 INRAE, University of Tours, Tours, France., Touzé A; 'Biologie des Infections à Polyomavirus' Team, UMR1282 INRAE, University of Tours, Tours, France., Schrama D; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany., Houben R; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany., Tabareau-Delalande F; Department of Pathology, Hospital Centrer of Orléans, Orléans, France., Neuhart A; Department of Biopathology, Center Léon Bérard, Lyon, France., de la Fouchardière A; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Biopathology, Center Léon Bérard, Lyon, France.; University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France., Osio A; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, Hospital Saint-Louis, AP-HP, Université Paris Cité, INSERM U976, Paris, France.; Centre National de Dermatopathologie, Paris-la Roquette, Ivry, France., Cavelier-Balloy B; Cabinet Mathurin Moreau, Paris, France., Laurent-Roussel S; Centre National de Dermatopathologie, Paris-la Roquette, Ivry, France.; Cabinet Mathurin Moreau, Paris, France., Sohier P; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, Hôpital Cochin, AP-HP, AP-HP.Centre - Université Paris Cité, Paris, France.; Faculté de Médecine, University Paris Cité, Paris, France., Cyprien T; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, Groupement des Hopitaux de l'institut catholique de Lille, Lille, France., Balme B; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, University Hospital of Lyon Sud, Lyon, France., Belzung F; Department of Pathology, University Hospital of Bordeaux, Bordeaux, France., Jullie ML; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, University Hospital of Bordeaux, Bordeaux, France., Cribier B; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Clinique Dermatologique, Hôpitaux Universitaires and Université de Strasbourg, Hôpital Civil, Strasbourg, France., Battistella M; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, Hospital Saint-Louis, AP-HP, Université Paris Cité, INSERM U976, Paris, France., Macagno N; CARADERM, French Network of Rare Cutaneous Cancer, Lille, France.; Department of Pathology, APHM, Timone University Hospital, Marseille, France.; Aix-Marseille University, INSERM U1251, MMG, Marseille, France.
Jazyk: angličtina
Zdroj: Histopathology [Histopathology] 2023 May; Vol. 82 (6), pp. 885-898. Date of Electronic Publication: 2023 Feb 22.
DOI: 10.1111/his.14874
Abstrakt: Aims: Recently, YAP1 fusion genes have been demonstrated in eccrine poroma and porocarcinoma, and the diagnostic use of YAP1 immunohistochemistry has been highlighted in this setting. In other organs, loss of YAP1 expression can reflect YAP1 rearrangement or transcriptional repression, notably through RB1 inactivation. In this context, our objective was to re-evaluate the performance of YAP1 immunohistochemistry for the diagnosis of poroma and porocarcinoma.
Methods and Results: The expression of the C-terminal part of the YAP1 protein was evaluated by immunohistochemistry in 543 cutaneous epithelial tumours, including 27 poromas, 14 porocarcinomas and 502 other cutaneous tumours. Tumours that showed a lack of expression of YAP1 were further investigated for Rb by immunohistochemistry and for fusion transcripts by real-time PCR (YAP1::MAML2 and YAP1::NUTM1). The absence of YAP1 expression was observed in 24 cases of poroma (89%), 10 porocarcinoma (72%), 162 Merkel cell carcinoma (98%), 14 squamous cell carcinoma (SCC) (15%), one trichoblastoma and one sebaceoma. Fusions of YAP1 were detected in only 16 cases of poroma (n = 66%), 10 porocarcinoma (71%) all lacking YAP1 expression, and in one sebaceoma. The loss of Rb expression was detected in all cases except one of YAP1-deficient SCC (n = 14), such tumours showing significant morphological overlap with porocarcinoma. In-vitro experiments in HaCat cells showed that RB1 knockdown resulted in repression of YAP1 protein expression.
Conclusion: In addition to gene fusion, we report that transcriptional repression of YAP1 can be observed in skin tumours with RB1 inactivation, including MCC and a subset of SCC.
(© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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