Deficient DNA mismatch repair and Nectin-4 expression in upper tract urothelial carcinoma (UTUC).

IF 2.8 3区 医学 Q3 ONCOLOGY
Peichen Duan, Le Yu, Yichang Hao, Shaohui Deng, Peng Hong, Min Lu, Shudong Zhang
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Abstract

Purpose: To investigate the prevalence of deficient DNA mismatch repair (dMMR) status in upper tract urothelial carcinoma (UTUC) and its association with clinicopathological characteristics as well as Nectin-4 immunohistochemical expression.

Methods: We retrospectively identified histologically confirmed UTUC cases treated at Peking University Third Hospital between December 2016 and September 2023. Eligible participants were required to also possess complete clinicopathological records and available formalin-fixed, paraffin-embedded (FFPE) tumor specimens suitable for immunohistochemical evaluation. MMR protein expression was categorized as either dMMR or proficient mismatch repair (pMMR), while Nectin-4 expression was quantitatively assessed using the H-score system. Samples were then classified as negative (H-score 0-14), low (H-score 15-99), medium (H-score 100-199), and high (H-score 200-300). Statistical significance was established at P < 0.05 using two-tailed tests.

Results: A total of 339 patients were deemed eligible, with specimens successfully evaluated. 25 patients (7.4%) demonstrated dMMR status. High Nectin-4 expression was observed in 124 patients (36.7%). A statistically significant association was identified between dMMR status and elevated Nectin-4 expression (P = 0.044). No significant differences were detected between dMMR and pMMR groups regarding clinical parameters, including gender, age, tumor grade, or immunophenotypic characteristics.

Conclusion: Our study revealed that 7.4% of UTUC patients exhibited dMMR status, with heterogeneous Nectin-4 expression observed across the cohort. Notably, we demonstrated a statistically significant correlation between dMMR status and elevated Nectin-4 expression, suggesting potential biological interplay. The combined biomarker profile warrants further investigation as a predictive tool for therapeutic strategies involving antibody-drug conjugates (e.g., enfortumab vedotin) and immune checkpoint inhibitors.

DNA错配修复缺陷和Nectin-4在上尿路上皮癌(UTUC)中的表达。
目的:探讨DNA错配修复缺陷(dMMR)在上尿路上皮癌(UTUC)中的患病率及其与临床病理特征和Nectin-4免疫组化表达的关系。方法:回顾性分析2016年12月至2023年9月在北京大学第三医院治疗的经组织学证实的UTUC病例。符合条件的参与者还需要拥有完整的临床病理记录和可用的福尔马林固定石蜡包埋(FFPE)肿瘤标本,适合免疫组织化学评估。MMR蛋白表达被分类为dMMR或熟练错配修复(pMMR),而Nectin-4表达使用h评分系统进行定量评估。然后将样本分为阴性(h -得分0-14)、低(h -得分15-99)、中(h -得分100-199)和高(h -得分200-300)。结果:共有339例患者被认为符合条件,标本被成功评估。25例患者(7.4%)表现为dMMR状态。124例患者中Nectin-4高表达(36.7%)。dMMR状态与Nectin-4表达升高有统计学意义(P = 0.044)。dMMR组和pMMR组在临床参数方面没有显著差异,包括性别、年龄、肿瘤分级或免疫表型特征。结论:我们的研究显示,7.4%的UTUC患者表现出dMMR状态,在整个队列中观察到异质Nectin-4表达。值得注意的是,我们证明dMMR状态与Nectin-4表达升高之间存在统计学上显著的相关性,表明可能存在生物学上的相互作用。联合生物标志物谱值得进一步研究,作为涉及抗体-药物偶联物(例如,enfortumab vedotin)和免疫检查点抑制剂的治疗策略的预测工具。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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