尿路上皮癌(UC)常规和亚型组织学分子异质性的进展、认识和解释:泌尿病理学家调查和文献综合回顾。
Advances, recognition, and interpretation of molecular heterogeneity among conventional and subtype histology of urothelial carcinoma (UC): a survey among urologic pathologists and comprehensive review of the literature.
发表日期:2024 Jul 29
作者:
Anandi Lobo, Katrina Collins, Seema Kaushal, Andres M Acosta, Mahmut Akgul, Amit K Adhya, Hikmat A Al-Ahmadie, Khaleel I Al-Obaidy, Ali Amin, Mahul B Amin, Manju Aron, Bonnie L Balzer, Rupanita Biswal, Subashish Mohanty, Lisa Browning, Indranil Chakrabarti, Luca Cima, Alessia Cimadamore, Sangeeta Desai, Jasreman Dhillon, Akansha Deshwal, Guillermo G Diego, Preeti Diwaker, Laurence A Galea, Cristina Magi-Galluzzi, Giovanna A Giannico, Nilesh S Gupta, Aiman Haider, Michelle S Hirsch, Kenneth A Iczkowski, Samriti Arora, Ekta Jain, Deepika Jain, Shilpy Jha, Shivani Kandukuri, Chia-Sui Kao, Oleksandr N Kryvenko, Ramani M Kumar, Niraj Kumari, Lakshmi P Kunju, Levente Kuthi, João Lobo, Jose I Lopez, Daniel J Luthringer, Fiona Maclean, Claudia Manini, Rahul Mannan, María G Martos, Rohit Mehra, Santosh Menon, Pritinanda Mishra, Holger Moch, Rodolfo Montironi, Manas R Baisakh, George J Netto, Lovelesh K Nigam, Adeboye O Osunkoya, Francesca Pagliuca, Gladell P Paner, Angel Panizo, Anil V Parwani, Maria M Picken, Susan Prendeville, Christopher G Przybycin, Suvendu Purkait, Francisco J Queipo, B Vishal Rao, Priya Rao, Victor E Reuter, Sankalp Sancheti, Ankur R Sangoi, Rohan Sardana, Swati Satturwar, Rajal B Shah, Shivani Sharma, Mallika Dixit, Monica Verma, Deepika Sirohi, Steven C Smith, Shailesh Soni, Sandhya Sundaram, Meenakshi Swain, Maria Tretiakova, Kiril Trpkov, Gorka MuñizUnamunzaga, Ming Zhou, Sean R Williamson, Antonio Lopez-Beltran, Liang Cheng, Sambit K Mohanty
来源:
HISTOPATHOLOGY
摘要:
尿路上皮癌(UC)表现出显着的分子和组织学异质性。 WHO 2022 分类暗示将分子特征添加到形态学诊断中。由于形态学和相关分子库可能会转化为治疗的选择和反应以及复发率,因此尿路病理学家需要更广泛地接受识别这些关键特征。这促使一项国际调查旨在确定全球泌尿病理学家中经典/亚型 UC 的实践模式。98 名泌尿病理学家使用 SurveyMonkey 软件共享了一项调查工具。对匿名受访者数据进行了分析。回应率为85%。大多数与管腔型 (93%) 和基础型 (82%) 的轮廓一致。对于 FGFR3 测试平台的看法各不相同。虽然 95% 的人同意 TERT 启动子突变是 UC 的关键驱动因素,但 72% 的人认为 APOBEC 突变是肌层浸润性膀胱癌 (MIBC) 的主要特征。泌尿病理学家对 MIBC 和 ERCC2 突变有不同的看法。在参与者中,94%的人会量化侵袭性微乳头状和肉瘤样组织学,而88%的人会重新评估具有微乳头状、小细胞或肉瘤样组织学的非肌层浸润性肿瘤中膀胱肿瘤标本的另一次经尿道切除术。大多数人同意微乳头(93%)、浆细胞样(97%)和小细胞(86%)亚型的特定分子特征。 96% 的参与者同意,小细胞成分预示着更具侵袭性的病程,应采用新辅助化疗进行治疗,63% 的参与者只会根据肿瘤科医生的要求对晚期肿瘤进行 HER2/neu 检测。 90% 的人同意,微卫星不稳定性测试虽然不是标准方案,但应考虑用于年轻的上尿路 UC 患者。 86% 的人同意具有高肿瘤突变负荷的 UC 将是免疫治疗的更好候选者。在精准医学时代,增强对 UC 分子异质性的了解将有助于更好的治疗选择、新的生物标志物发现、创新的管理方案和结果。我们的调查提供了病理学家关于将组织分子方法纳入“个性化”治疗的看法和经验的广阔视角。由于临床采用情况各异,需要使用统一研究标准获得额外数据。这将推动该领域最佳实践指南的产生,以实现广泛且一致的临床实用性。© 2024 John Wiley
Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe.A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy.In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.© 2024 John Wiley & Sons Ltd.