Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants
Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants
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DOI：
10.1016/j.eururo.2018.09.003
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发表时间：
2019-01-01
期刊：
影响因子：
23.4
通讯作者：
DeGraff, David J.
中科院分区：
文献类型：
--
作者：
Warrick, Joshua I.;Sjodahl, Gottfrid;DeGraff, David J.
分子亚型可以为膀胱癌的预后和治疗反应提供信息。然而，肿瘤内的分子异质性在这种疾病中没有得到很好的研究，可能会使使用分子亚型指导患者管理的努力复杂化。为了研究膀胱癌的肿瘤内异质性，我们在一个连续的、回顾性的膀胱癌组织学变异系列和与之同时发生的传统尿路上皮癌中检测了分子亚型。根据隆德大学报告的方法分配分子亚型，该方法结合了细胞周期改变和分化标志物，以得到尿路上皮样、基因组不稳定、基底鳞状、间充质样和神经内分泌样亚型。大多数（93%）肿瘤被归类为尿路上皮样，基因组不稳定，或基底鳞状。在具有一种以上肿瘤组织学的患者中，39%的患者表现出不同肿瘤组织学之间的分子异质性。基底-鳞状细胞癌亚型的比例最高，其中78%与尿路上皮样癌或基因组不稳定癌（在多种组织学类型的病例中）同时发生。与此相反，没有共同发生的尿路上皮样癌和基因组不稳定癌在同一患者。研究结果表明，膀胱癌往往是分子异质性，特别是在基底鳞状亚型。这引起了人们对实验室检测中的抽样误差的关注，这些实验室检测指导基于分子亚型的治疗。患者摘要：在这份报告中，我们调查了膀胱癌患者同一肿瘤不同区域之间的分子多样性。我们发现同一肿瘤的不同区域在分子水平上往往是不同的。我们的结论是，这种生物多样性必须考虑到在解释膀胱癌样本的临床分子检测。(C)2018年欧洲泌尿外科协会。Elsevier B. V.出版，保留所有权利。
Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93%) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39% demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78% of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping.Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.