不同的规则导致YAP1在汗管瘤、汗管癌和RB1缺失皮肤癌中表达丧失。
Distinct regulations driving YAP1 expression loss in poroma, porocarcinoma and RB1-deficient skin carcinoma.
发表日期：2023 Jan 31
作者：
Thibault Kervarrec, Eric Frouin, Christine Collin, Anne Tallet, Matthias Tallegas, Daniel Pissaloux, Franck Tirode, Serge Guyétant, Mahtab Samimi, Pauline Gaboriaud, Antoine Touzé, David Schrama, Roland Houben, Flore Tabareau-Delalande, Anne Neuhart, Arnaud de la Fouchardière, Amélie Osio, Bénédicte Cavelier-Balloy, Sara Laurent-Roussel, Pierre Sohier, Tilmant Cyprien, Brigitte Balme, Fanny Belzung, Marie-Laure Jullie, Bernard Cribier, Maxime Battistella, Nicolas Macagno
来源：
HISTOPATHOLOGY
摘要：
最近，在汗腺瘤和汗腺癌中已经证实了YAP1融合基因，并且在这种情况下，YAP1免疫组织化学诊断的使用已经引起了关注。在其他器官中，YAP1表达的丧失可能反映出YAP1重组或转录抑制，特别是通过RB1失活。在这种背景下，我们的目标是重新评估YAP1免疫组织化学诊断对于汗腺瘤和汗腺癌的诊断性能。在包括27个汗腺瘤、14个汗腺癌和502个其他皮肤肿瘤的543个皮肤上皮肿瘤中，通过免疫组织化学评估YAP1蛋白的C端部分的表达情况。表明缺乏YAP1表达的肿瘤进一步通过免疫组织化学和实时PCR（YAP1::MAML2和YAP1::NUTM1）进行了研究。在24例汗腺瘤（89%）、10例汗腺癌（72%）、162例默克尔细胞癌（98%）、14例鳞癌（15%）、一例毛囊母细胞瘤和一例皮脂腺瘤中观察到了缺乏YAP1表达。 YAP1的融合仅在16例汗腺瘤（n = 66%）、10例汗腺癌（71%）中被检测到，这些肿瘤都缺乏YAP1表达，并在一例皮脂腺瘤中被检测到。在YAP1缺乏的SCC（n = 14）案例中，除了一个之外，所有案例都检测到Rb表达的丧失，这些肿瘤与汗腺癌存在明显的形态学重叠。在HaCat细胞中的体外实验表明，RB1敲除导致YAP1蛋白表达抑制。除了基因融合之外，我们报告了在RB1失活的皮肤肿瘤中观察到YAP1的转录抑制，包括MCC和一部分SCC。© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.
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.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.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.