{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:03:50Z","timestamp":1791187430682,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Purpose<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n A multicenter registry study (April 2023\u2013March 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\u201067).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 1054 patients, 18.6% were HER2\u2010negative (IHC 0), 23.0% were HER2\u2010low (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+,\n p<\/jats:italic>\n \u2009<\u20090.001), infiltrative tumors (61.1% in IHC 2+\/3+,\n p<\/jats:italic>\n \u2009<\u20090.001), and high\u2010grade tumors (62.5% in IHC 2+\/3+,\n p<\/jats:italic>\n \u2009<\u20090.001). In a sub\u2010analysis comparing HER2\u2010low (1+) and HER2\u2010overexpressing (2+\/3+) groups, multivariable logistic regression confirmed bladder primary site (OR\u2009=\u20091.783,\n p<\/jats:italic>\n \u2009=\u20090.001), infiltrative status (OR\u2009=\u20091.492,\n p<\/jats:italic>\n \u2009=\u20090.027), and high\u2010grade differentiation (OR\u2009=\u20091.918,\n p<\/jats:italic>\n \u2009=\u20090.001) as independent predictors of HER2 overexpression, though the model's predictive ability was modest (AUC\u2009=\u20090.64). Expression of CK20, GATA3, P16, and Uroplakin3 also differed significantly between HER2\u2010negative and HER2\u2010positive groups.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study delineates distinct clinicopathological profiles for HER2\u2010negative, HER2\u2010low, and HER2\u2010overexpressing UC in Chinese patients. These findings provide a crucial evidence base for refining personalized treatment strategies, particularly for HER2\u2010targeted therapies like antibody\u2010drug conjugates (ADCs), across the entire spectrum of HER2 expression.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.71289","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:59:28Z","timestamp":1760101168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Distinct Clinicopathological Features of\n HER2<\/scp>\n \u2010Negative,\n HER2<\/scp>\n \u2010Low, and\n HER2<\/scp>\n \u2010Overexpressing Urothelial Carcinoma in a Large Chinese Cohort"],"prefix":"10.1002","volume":"14","author":[{"given":"Shanshan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-5195","authenticated-orcid":false,"given":"Dingwei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Urology Renmin Hospital of Wuhan University (Hubei General Hospital) Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology Henan Cancer Hospital Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0218-3288","authenticated-orcid":false,"given":"Xiaoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The Affiliated Tumor Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University Cancer Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-016-1928-x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djad246"},{"issue":"10","key":"e_1_2_11_5_1","first-page":"10001","article-title":"Clinical Pathology Expert Consensus on HER2 Testing in Chinese Urothelial Carcinoma","volume":"43","author":"Chinese Society of Pathology, Chinese Anti\u2010Cancer Association Genitourinary Cancer Committee, & Chinese Society of Clinical Oncology's Expert Committee on Urothelial Cancer","year":"2021","journal-title":"Chinese Journal of Oncology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.5_suppl.795"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.4509"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.4519"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02005"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1355081"},{"issue":"11","key":"e_1_2_11_11_1","first-page":"1011","article-title":"Correlation of HER2 Expression and Clinicopathological Characteristics in Patients With Urothelial Carcinoma in China","volume":"34","author":"Wang S.","year":"2024","journal-title":"China Oncology"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1011885"},{"issue":"6","key":"e_1_2_11_13_1","first-page":"951","article-title":"Next\u2010Generation Sequencing of Advanced Urothelial Carcinoma: A Prospective, Single\u2010Institution Study","volume":"72","author":"Pietzak E. J.","year":"2017","journal-title":"European Urology"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2025.100753"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.4569"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyae127"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2021.10.006"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:11:27Z","timestamp":1765285887000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.71289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":16,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/cam4.71289"],"URL":"https:\/\/doi.org\/10.1002\/cam4.71289","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71289"}}