Risk factors and therapeutic significance of HER2 overexpression in urothelial carcinoma

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-06-09 DOI:10.1016/j.prp.2025.156079

Chunjin Ke , Jie Wan , Guoping Wang , Zhiquan Hu , Chunguang Yang

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Abstract

Objective

We analyzed the expression of HER2 in urothelial carcinoma (UC) and the risk factors for overexpression, and then further explored the guiding significance of HER2 in the treatment of locally progressive and advanced UC.People's Republic of China

Methods

Immunohistochemistry (IHC) was used to detect HER2, luminal markers (CK20, GATA3), and basal markers (CK5/6, CD44). HER2 overexpression was defined as IHC 2 + or IHC 3 + . Binary logistic regression was used to analyze the risk factors for HER2 overexpression. The therapeutic significance of HER2 was preliminarily discussed through case analysis.

Results

A total of 119 patients with UC were included in this study, including 99 males and 20 females, with an average age of 66.2 ± 9.6 years. UC were derived from the bladder [n = 97 (81.5 %)], renal pelvis [n = 15 (12.6 %)], ureter [n = 6 (5.0 %)] and prostate [n = 1 (0.8 %)], respectively. UC were classified according to molecular typing into luminal 76 (63.9 %) cases and basal 29 (24.4 %) cases. HER2 expression rates of IHC 0, 1 + , 2 + , and 3 + in UC were 39.5 %, 23.5 %, 31.9 %, and 5 %, respectively. HER2 overexpression was as high as 52.6 % in luminal patients, but only 3.4 % in basal patients (53.2 % vs 3.4 %, P < 0.001). HER2 overexpression was strongly correlated with lower urinary tract, invasive, high-grade, multiple tumors and luminal (P < 0.05), while no significant correlation was seen with patients' gender (P = 0.311), age (P = 0.722), lymph node metastasis (P = 0.282) and ki67 index (P = 0.964). Multiple tumors (OR=5.346, 95 %CI: 1.921–14.877, P = 0.001) and luminal (OR=28.827, 95 %CI: 2.768–300.225, P = 0.005) were independent risk factors for HER2 overexpression. cT2N0M0 patient with HER2 (2 +) showed significant tumor shrinkage after preoperative neoadjuvant therapy with RC48-ADC.

Conclusions

HER2 testing can be routinely done in patients with locally advanced or metastatic UC, multiple tumors and luminal. Neoadjuvant therapy (HER2-ADC) for locally advanced UC was found to significantly shrink tumors, providing a theoretical basis for organ preservation and functional protection in genitourinary tumor surgery. HER2-ADC may be effective and safe in the treatment of locally progressive or advanced UC.

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尿路上皮癌中HER2过表达的危险因素及治疗意义

目的分析HER2在尿路上皮癌（UC）中的表达及过表达的危险因素，进一步探讨HER2在局部进展和晚期UC治疗中的指导意义。方法免疫组织化学（IHC）检测HER2、腔内标记物（CK20、GATA3）和基础标记物（CK5/6、CD44）。HER2过表达定义为IHC 2 + 或IHC 3 + 。采用二元logistic回归分析HER2过表达的危险因素。通过病例分析，初步探讨了HER2的治疗意义。结果本研究共纳入119例UC患者，其中男性99例，女性20例，平均年龄66.2 ± 9.6岁。加州大学来自膀胱[n = 97(81.5 %)],肾盂[n = 15(12.6 %)],输尿管[n = 6(5.0 %)]和前列腺[n = 1(0.8 %)],分别。根据分子分型将UC分为腔内76例（63.9 %）和基底29例（24.4 %）。HER2表达率包含IHC 0,1 + 2 + ,和3 + UC % 39.5,23.5 % 31.9 %,分别和5 %。HER2过表达在管腔患者中高达52.6% %，而在基础患者中仅为3.4 %（53.2 % vs 3.4 %,P <； 0.001）。HER2过度强烈与降低尿路,入侵,高档,多个肿瘤和鲁米那(P & lt; 0.05),尽管没有明显的相关性被认为与患者的性别(P = 0.311)、年龄(P = 0.722),淋巴结转移(P = 0.282)和ki67指数(P = 0.964)。多发性肿瘤（OR=5.346, 95 %CI: 1.921-14.877, P = 0.001）和腹腔（OR=28.827, 95 %CI: 2.768-300.225, P = 0.005）是HER2过表达的独立危险因素。cT2N0M0 HER2患者（2 +）术前经RC48-ADC新辅助治疗后肿瘤明显缩小。结论在局部晚期或转移性UC、多发性肿瘤及管腔性UC患者中，可常规进行sher2检测。新辅助治疗（HER2-ADC）治疗局部晚期UC可显著缩小肿瘤，为泌尿生殖系统肿瘤手术器官保存和功能保护提供理论依据。HER2-ADC治疗局部进展性或晚期UC可能是有效和安全的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.