当前位置: X-MOL 学术Cell. Oncol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Pure high-grade papillary urothelial bladder cancer: a luminal-like subgroup with potential for targeted therapy.
Cellular Oncology ( IF 4.9 ) Pub Date : 2020-05-22 , DOI: 10.1007/s13402-020-00524-6
Tician Schnitzler 1 , Nadina Ortiz-Brüchle 1 , Ursula Schneider 1 , Isabella Lurje 1 , Karolina Guricova 1 , Alexander Buchner 2 , Gerald Bastian Schulz 2 , Axel Heidenreich 3, 4 , Nadine Therese Gaisa 1 , Ruth Knüchel 1 , Stefan Garczyk 1
Affiliation  

PURPOSE Non-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guérin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy. METHODS An immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved. RESULTS We found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration. CONCLUSIONS Our data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.

中文翻译:


纯高级别乳头状尿路上皮膀胱癌:具有靶向治疗潜力的管腔样亚组。



目的非侵袭性高级别(HG)膀胱癌是一种异质性疾病,其特征尚不充分。一线卡介苗滴注在大量病例中失败,替代的膀胱保留治疗也很有限,这凸显了促进对非侵入性 HG 病变进一步分子了解的必要性。在这里,我们对纯 HG 乳头状尿路上皮膀胱癌(纯 pTa HG)进行了表征,该癌是非侵袭性 HG 膀胱癌的一个潜在亚组,涉及分子亚型隶属关系和靶向治疗的潜力。方法 使用包含管腔标记(KRT20、ERBB2、ESR2、GATA3)和基础标记(KRT5/6、KRT14)以及 p53 和 FGFR3 的免疫组织化学组来分析 78 个纯 pTa HG/乳头状 pT1(a) HG 的分子亚型隶属关系样品。其中 66 例进行了 ERBB2 荧光原位杂交。此外,还对 19 个 pTa HG 病例进行了靶向测序(31 个基因),重点关注已知的治疗靶点或那些描述用于预测注册临床试验中提到的或已批准的靶向治疗的反应的靶点。结果我们发现,纯 pTa HG/乳头状 pT1(a) HG 病变的特征是管腔样表型,与频繁(58% 的样本)中等到高 ERBB2 蛋白表达、基因组和蛋白水平上罕见的 FGFR3 改变以及高频率(89% 的样本)染色质修饰基因改变。值得注意的是,95% 的 pTa HG/乳头状 pT1 HG 病例至少存在一种潜在的可药物基因组改变。结论 我们的数据应有助于指导未来临床试验中研究的靶向治疗的选择,此外,还可以为 pTa HG 发病机制的前瞻性机制研究提供基础。
更新日期:2020-05-22
down
wechat
bug