Distinct Clinicopathological Features of HER2-Negative, HER2-Low, and HER2-Overexpressing Urothelial Carcinoma in a Large Chinese Cohort

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-10-10 DOI:10.1002/cam4.71289

Shanshan Wang, Dingwei Ye, Li Yang, Fan Cheng, Tiejun Yang, Xiaoping Zhang, Zhixian Yu, Qingyun Zhang, Yong Yang

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Abstract

Purpose

To investigate the expression patterns of Human Epidermal Growth Factor Receptor 2 (HER2) and their clinicopathological associations across the full spectrum (negative, low, and overexpression) in a large cohort of Chinese urothelial carcinoma (UC) patients.

Materials and Methods

A multicenter registry study (April 2023–March 2024) across eight Chinese tertiary hospitals included 1054 UC patients. Demographic, clinical, and pathological data were analyzed to identify factors associated with different HER2 expression levels (IHC 0 vs. 1+ vs. 2+/3+). A subset of patients was evaluated for additional IHC markers (e.g., CK20, GATA3, P16, Uroplakin3, Ki-67).

Results

Of 1054 patients, 18.6% were HER2-negative (IHC 0), 23.0% were HER2-low (IHC 1+), and 58.4% exhibited HER2 overexpression (IHC 2+/3+). Increasing HER2 expression was significantly associated with bladder tumor location (63.1% in IHC 2+/3+, p < 0.001), infiltrative tumors (61.1% in IHC 2+/3+, p < 0.001), and high-grade tumors (62.5% in IHC 2+/3+, p < 0.001). In a sub-analysis comparing HER2-low (1+) and HER2-overexpressing (2+/3+) groups, multivariable logistic regression confirmed bladder primary site (OR = 1.783, p = 0.001), infiltrative status (OR = 1.492, p = 0.027), and high-grade differentiation (OR = 1.918, p = 0.001) as independent predictors of HER2 overexpression, though the model's predictive ability was modest (AUC = 0.64). Expression of CK20, GATA3, P16, and Uroplakin3 also differed significantly between HER2-negative and HER2-positive groups.

Conclusions

This study delineates distinct clinicopathological profiles for HER2-negative, HER2-low, and HER2-overexpressing UC in Chinese patients. These findings provide a crucial evidence base for refining personalized treatment strategies, particularly for HER2-targeted therapies like antibody-drug conjugates (ADCs), across the entire spectrum of HER2 expression.

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在一个大型中国队列中，her2阴性、her2低表达和her2过表达尿路上皮癌的不同临床病理特征

目的探讨人表皮生长因子受体2 （HER2）在中国尿路上皮癌（UC）患者全谱（阴性、低表达和过表达）中的表达模式及其临床病理相关性。材料与方法一项多中心注册研究（2023年4月- 2024年3月）在中国8家三级医院进行，包括1054例UC患者。对人口统计学、临床和病理数据进行分析，以确定与不同HER2表达水平相关的因素（IHC 0、1+、2+/3+）。对一部分患者进行额外的免疫组化标志物评估（如CK20、GATA3、P16、Uroplakin3、Ki-67）。结果1054例患者中，18.6%为HER2阴性（IHC 0）， 23.0%为HER2低表达（IHC 1+）， 58.4%为HER2过表达（IHC 2+/3+）。HER2表达升高与膀胱肿瘤定位（IHC 2+/3+组63.1%,p < 0.001）、浸润性肿瘤（IHC 2+/3+组61.1%,p < 0.001）、高级别肿瘤（IHC 2+/3+组62.5%,p < 0.001）显著相关。在比较HER2低（1+）和HER2过表达（2+/3+）组的亚分析中，多变量logistic回归证实膀胱原发部位（OR = 1.783, p = 0.001）、浸润状态（OR = 1.492, p = 0.027）和高度分化（OR = 1.918, p = 0.001）是HER2过表达的独立预测因子，尽管该模型的预测能力一般（AUC = 0.64）。在her2阴性组和her2阳性组中，CK20、GATA3、P16和Uroplakin3的表达也有显著差异。本研究描述了中国患者her2阴性、her2低表达和her2过表达UC的不同临床病理特征。这些发现为完善个性化治疗策略提供了重要的证据基础，特别是对于HER2靶向治疗，如抗体-药物偶联物（adc），适用于整个HER2表达谱。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.