Shanshan Wang, Dingwei Ye, Li Yang, Fan Cheng, Tiejun Yang, Xiaoping Zhang, Zhixian Yu, Qingyun Zhang, Yong Yang
{"title":"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","authors":"Shanshan Wang, Dingwei Ye, Li Yang, Fan Cheng, Tiejun Yang, Xiaoping Zhang, Zhixian Yu, Qingyun Zhang, Yong Yang","doi":"10.1002/cam4.71289","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Purpose</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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+, <i>p</i> < 0.001), infiltrative tumors (61.1% in IHC 2+/3+, <i>p</i> < 0.001), and high-grade tumors (62.5% in IHC 2+/3+, <i>p</i> < 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, <i>p</i> = 0.001), infiltrative status (OR = 1.492, <i>p</i> = 0.027), and high-grade differentiation (OR = 1.918, <i>p</i> = 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 19","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71289","citationCount":"0","resultStr":"{\"title\":\"Distinct Clinicopathological Features of HER2-Negative, HER2-Low, and HER2-Overexpressing Urothelial Carcinoma in a Large Chinese Cohort\",\"authors\":\"Shanshan Wang, Dingwei Ye, Li Yang, Fan Cheng, Tiejun Yang, Xiaoping Zhang, Zhixian Yu, Qingyun Zhang, Yong Yang\",\"doi\":\"10.1002/cam4.71289\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Purpose</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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+, <i>p</i> < 0.001), infiltrative tumors (61.1% in IHC 2+/3+, <i>p</i> < 0.001), and high-grade tumors (62.5% in IHC 2+/3+, <i>p</i> < 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, <i>p</i> = 0.001), infiltrative status (OR = 1.492, <i>p</i> = 0.027), and high-grade differentiation (OR = 1.918, <i>p</i> = 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>This study delineates distinct clinicopathological profiles for HER2-negative, HER2-low, and HER2-overexpressing UC in Chinese patients. 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Distinct Clinicopathological Features of HER2-Negative, HER2-Low, and HER2-Overexpressing Urothelial Carcinoma in a Large Chinese Cohort
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.
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.
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