上道泌尿道癌的转录基因分析:膀癌共识分类相关性,分子异质性和差异性免疫特征
Jacqueline Fontugne1, Evanguelos Xylinas2, Clémentine Krucker3
1Department of Pathology, Institut Curie, Saint-Cloud, France; Institut Curie, CNRS, UMR144, Equipe labellisée Ligue Contre le Cancer, Paris Sciences et Lettres Research University, Paris, France; Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.
概括
肌肉侵入性膀癌 (MIBC) 的共识分类有效地对上道泌尿道癌 (UTUC) 进行了分类,在UTUC中显示出较高比例的光线 papillary (LumP) 亚型. LumP UTUCs经常表现出较低的免疫透率和高的FGFR3突变率,这表明与MIBC相比,治疗反应不同.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子病理学分子病理学
背景情况:
- 肌肉侵入性膀癌 (MIBC) 具有共识的分子分类,但上道泌尿道癌 (UTUC) 仍然不太了解.
- 描述UTUC分子亚型对于理解疾病行为和指导治疗策略至关重要.
研究的目的:
- 确定MIBC共识分类在UTUC中的相关性.
- 在一组手术治疗的UTUC (≥pT1) 中,描述分子亚型和内异质性.
主要方法:
- 免疫组织化学 (IHC) 用于亚型标记物,p16,Ki67,不匹配修复蛋白和PD-L1.
- 通过火烧测序和3'RNA测序进行FGFR3突变分析.
- 对共识类,无监督组和微环境细胞丰度的基因表达分析.
主要成果:
- 在MIBC共识分类中,UTUCs被强有力的分类,而光皮质 (LumP) 是主要的亚型,特别是在≥pT2瘤中 (57.2%).
- 在40%的UTUC中发现了FGFR3突变;LumP瘤经常存在这些突变,并显示出低免疫透和PD-L1表达.
- 在15.2%的病例中观察到内异质性,共识类与FGFR3突变,阶段,形态和IHC标志物相关.
结论:
- 与MIBC相比,MIBC共识分类适用于UTUC,突出显示LumP亚型的流行率较高.
- LumP UTUC,特别是那些具有 FGFR3 突变的,具有较低的免疫透率和 PD-L1 表达的特征.
- 这些分子差异表明,与MIBC相比,UTUC可能对新疗法做出不同的反应.
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