adc时代具有膀胱癌阳性病史的上尿路上皮癌与仅UTUC的分子谱(Nectin-4和TROP-2)比较

IF 3.4 2区 医学 Q2 ONCOLOGY
Mohammed Rafea Kanaan, Jessica Schmitz, Jan Hinrich Braesen, Markus Antonius Kuczyk, Hossein Tezval
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引用次数: 0

摘要

上路尿路上皮癌(UTUC)和膀胱癌(UBC)虽然在组织学上相似,但在分子上不同,这促使人们对它们的生物标志物谱进行靶向治疗,如抗体-药物偶联物(adc) enfortumab vedotin(靶向Nectin-4)和sacituzumab govitecan(靶向TROP-2)。本研究调查了87例UTUC患者中Nectin-4和TROP-2的表达,其中54例合并UBC (UTUC + UBC), 33例合并UTUC。免疫组织化学分析显示广泛的TROP-2表达(98.8%的样本),高水平与低级别UTUC (p = 0.043)和高染色(平均h评分227±63)相关。Nectin-4在70.1%的样本中表达,但在UTUC + UBC组中表达频率更高(88.8%对63.6%),尽管这种差异缺乏统计学意义(p = 0.340)。值得注意的是,两组的Nectin-4染色强度较弱(平均h值66±65),提示UTUC伴UBC和不伴UBC之间存在生物学差异。研究结果表明,靶向TROP-2和Nectin-4的adc可能在不需要事先进行生物标志物检测的情况下,在UTUC中具有治疗前景。此外,在UTUC + UBC患者中升高的Nectin-4表达暗示不同的分子途径可能影响治疗策略,值得进一步的临床探索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparison of molecular profiles (Nectin-4 and TROP-2) in upper tract urothelial carcinoma with a positive history of urinary bladder cancer vs. UTUC only in the era of ADCs.

Upper tract urothelial carcinoma (UTUC) and urinary bladder cancer (UBC), though histologically similar, differ molecularly, prompting interest in their biomarker profiles for targeted therapies like antibody-drug conjugates (ADCs) enfortumab vedotin (targeting Nectin-4) and sacituzumab govitecan (targeting TROP-2). This study investigated Nectin-4 and TROP-2 expression in 87 UTUC patients, including 54 with a history of concurrent UBC (UTUC + UBC) and 33 with UTUC alone. Immunohistochemical analysis revealed widespread TROP-2 expression (98.8% of samples), with high levels linked to low-grade UTUC (p = 0.043) and intense staining (mean H-score 227 ± 63) across both cohorts. Nectin-4 was expressed in 70.1% of samples overall but was more frequent in the UTUC + UBC group (88.8% vs. 63.6% in UTUC-only patients), though this difference lacked statistical significance (p = 0.340). Notably, Nectin-4 staining intensity was weak in both groups (mean H-score 66 ± 65), suggesting biological distinctions between UTUC with and without UBC. The findings imply that ADCs targeting TROP-2 and Nectin-4 may hold therapeutic promise in UTUC without requiring prior biomarker testing. Additionally, the elevated Nectin-4 expression in UTUC + UBC patients hints at divergent molecular pathways that could influence treatment strategies, warranting further clinical exploration.

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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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