具有分化分化的膀胱癌 (BCDD) 是一组预后不良的异质性肿瘤，据报道 BCDD 中 nectin-4 和程序性死亡配体-1 (PD-L1) 存在差异表达。重要的是，膀胱癌中的 nectin-4 表达与 enfortumab vedotin 的反应相关，PD-L1 表达与免疫检查点抑制剂 (ICIs) 的反应相关。作者进行了一项回顾性审查，确定了 117 名晚期或转移性 BCDD 患者，这些患者2011年至2021年在Winship癌症研究所接受治疗。他们对这些患者的组织学亚型进行了nectin-4和PD-L1表达的免疫组织化学染色，并对这些患者进行了基因组分析，包括RNA测序、全外显子组测序和融合检测分析作为接受 ICI 的 BCDD 患者的亚组基因组分析。结果表明，nectin-4 表达在鳞状细胞和浆细胞样亚型组中最高，而肉瘤样亚型组（70.8%）比例最高PD-L1 阳性患者。基因组分析得出了几项关键发现，包括小细胞 BCDD 患者的 RB1 突变率为 50%、跨 BCDD 多个亚型的可靶向 PIK3CA 突变，以及 ICI 应答者中 TEC 的表达显着较高。罕见膀胱肿瘤患者中nectin-4和PD-L1表达的相关数据。他们还在基因组分析中发现了一些新发现，强调了精准医疗在这一患者群体中的作用。需要更大规模的前瞻性研究来验证这些假设生成数据。© 2024 美国癌症协会。

Bladder cancer with divergent differentiation (BCDD) comprises a heterogenous group of tumors with a poor prognosis, and differential expression of nectin-4 and programmed death ligand-1 (PD-L1) has been reported in BCDD. Importantly, nectin-4 expression in bladder cancer is associated with response to enfortumab vedotin, and PD-L1 expression is associated with responses to immune checkpoint inhibitors (ICIs).The authors conducted a retrospective review identifying 117 patients with advanced or metastatic BCDD who were treated at Winship Cancer Institute from 2011 to 2021. They performed immunohistochemistry staining for nectin-4 and PD-L1 expression by histologic subtype as well as genomic analysis of these patients, including RNA sequencing, whole-exome sequencing, and fusion detection analysis as well as a subgroup genomic analysis of patients with BCDD who received ICIs.The results indicated that nectin-4 expression was highest in the groups who had the squamous and plasmacytoid subtypes, whereas the group that had the sarcomatoid subtype (70.8%) had the highest proportion of PD-L1-positive patients. Genomic analysis yielded several key findings, including a 50% RB1 mutation rate in patients who had small cell BCDD, targetable PIK3CA mutations across multiple subtypes of BCDD, and significantly higher expression of TEC in responders to ICIs.In this study, the authors identified clinically relevant data on nectin-4 and PD-L1 expression in patients with rare bladder tumors. They also identified several novel findings in the genomic analysis that highlight the role of precision medicine in this population of patients. Larger, prospective studies are needed to validate these hypothesis-generating data.© 2024 American Cancer Society.