中国尿路上皮癌患者HER2表达及其与临床病理学特征的关联分析

王珊珊; 叶定伟; 杨立; 程帆; 杨铁军; 章小平; 余志贤; 张庆云; 杨勇

doi:10.19401/j.cnki.1007-3639.2024.11.003

您当前的位置：

首页 >

文章列表页 >

中国尿路上皮癌患者HER2表达及其与临床病理学特征的关联分析

论著 | 更新时间：2025-12-31

- 中国尿路上皮癌患者HER2表达及其与临床病理学特征的关联分析
- Correlation of HER2 expression and clinicopathological characteristics in patients with urothelial carcinoma in China
- 中国癌症杂志 2024年34卷第11期页码：1011-1019
- 作者机构：
  
  1. 复旦大学附属肿瘤医院泌尿外科，复旦大学上海医学院肿瘤学系，上海 200032
  2. 兰州大学第二医院泌尿外科，甘肃兰州 730030
  3. 武汉大学人民医院（湖北省人民医院）泌尿外科，湖北武汉 430060
  4. 河南省肿瘤医院泌尿外科，河南郑州 450003
  5. 华中科技大学同济医学院附属协和医院泌尿外科，湖北武汉 430090
  6. 温州医科大学附属第一医院泌尿外科，浙江温州 325000
  7. 广西医科大学附属肿瘤医院泌尿外科，广西南宁 530000
  8. 北京大学肿瘤医院泌尿外科，北京 100142
- 作者简介：
  
  [ "王珊珊（ORCID: 0000-0002-6651-2821），博士，主治医师。" ]
  叶定伟（ORCID: 0000-0002-6761-5195），博士，主任医师，复旦大学附属肿瘤医院党委副书记、泌尿外科学科带头人。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.11.003
  中图分类号： R737.1
- 收稿：2024-07-15，
  
  修回：2024-11-15，
  
  纸质出版：2024-11-30
- 稿件说明：
移动端阅览
王珊珊, 叶定伟, 杨立, 等. 中国尿路上皮癌患者HER2表达及其与临床病理学特征的关联分析[J]. 中国癌症杂志, 2024,34(11):1011-1019.

Shanshan WANG, Dingwei YE, Li YANG, et al. Correlation of HER2 expression and clinicopathological characteristics in patients with urothelial carcinoma in China[J]. China Oncology, 2024, 34(11): 1011-1019.
王珊珊, 叶定伟, 杨立, 等. 中国尿路上皮癌患者HER2表达及其与临床病理学特征的关联分析[J]. 中国癌症杂志, 2024,34(11):1011-1019. DOI： 10.19401/j.cnki.1007-3639.2024.11.003.

Shanshan WANG, Dingwei YE, Li YANG, et al. Correlation of HER2 expression and clinicopathological characteristics in patients with urothelial carcinoma in China[J]. China Oncology, 2024, 34(11): 1011-1019. DOI： 10.19401/j.cnki.1007-3639.2024.11.003.

摘要

背景：

人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）与尿路上皮癌（urothelial carcinoma，UC）的疗效及患者预后密切相关。HER2是多种肿瘤的重要生物标志物和治疗靶点，抗HER2抗体药物偶联物对HER2过表达的UC患者具有显著的临床疗效，因此深入了解中国UC患者HER2表达及其特点，对于指导治疗决策、优化治疗方案和实现个体化治疗具有重要意义。本研究旨在充分探究中国UC患者的HER2表达情况及其与临床病理学特征的相关性。

方法：

本研究是一项多中心研究，回顾性纳入了中国5个地理区域（华北、华东、华南、华中和西北）共8个三甲医院的泌尿外科2023年1月—2024年3月采集组织样本的UC患者。纳入标准：① 年龄18岁以上；② 经组织病理学或细胞学检查确诊的UC；③ 需有肿瘤原发灶免疫组织化学（immunohistochemistry，IHC）检测HER2表达的完整资料。排除标准：① 已确诊合并其他部位肿瘤者；② 医师评估其他不适合纳入本研究的情况。收集患者的HER2 IHC检测结果及疾病信息，根据《中国尿路上皮癌人表皮生长因子受体2检测临床病理专家共识》的标准对HER2表达进行判读，将HER2 2＋及3＋定义为HER2过表达。分析HER2的表达情况及其与临床病理学特征的关联。本研究已获得复旦大学附属肿瘤医院医学伦理委员会批准（伦理编号：2301268-12），并于中国临床试验注册中心注册（注册编号：ChiCTR2300069746）。

结果：

共纳入1 054例UC患者，其中以膀胱UC为主（

=807，76.6%），平均年龄为（66.8±10.5）岁，多数（78.5%）患者为男性。HER2过表达率为58.4%（

=616），此外还有23%的患者为HER2 1＋表达（

=242），少数（

=196，18.6%）患者为HER2零表达。HER2表达与多种临床病理学特征存在显著关联，包括美国东部肿瘤协作组（Eastern Cooperative Oncology Group，ECOG）评分、心脑血管疾病病史、脂代谢病病史、吸烟史、UC疾病部位、分化程度、病理学类型和肿瘤分期。

结论：

本多中心回顾性分析显示，中国UC患者中HER

2表达普遍存在，过表达率达58.4%，并且HER2表达与多种临床病理学特征密切相关。因此，准确评估UC患者的HER2表达对于指导个体化治疗具有重要意义。

Abstract

Background and purpose:

Human epidermal growth factor receptor 2 (HER2) is closely associated with drug efficacy and prognosis in urothelial carcinoma (UC). HER2 is a significant biomarker and therapeutic target in various tumors. In recent years

anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression. Therefore

an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making

optimize treatment strategies and achieve personalized therapy. This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.

Methods:

This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China (North China

East China

South China

Central China and Northwest) whose tissue samples were collected from January 2023 to March 2024. Inclusion criteria: ① age above 18 years; ② UC diagnosed by histopathological or cytological examination; ③ complete results of HER2 expression detection using immunohistochemistry (IHC) in the primary tumor site were required. Exclusion criteria: ① diagnosed patients with tumors in other parts of the body; ② physicians evaluated other situations that were not suitable for inclusion in this study. IHC results for HER2 expression and clinicopathological data were collected. HER2 expression was determined according to the criteria outlined in “Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China”

with HER2 2＋ and 3＋ defined as HER2 overexpression. The HER2 expression and clinicopathological features were analyzed. This study was approved by the medical ethics committee of Fudan Univ

ersity Shanghai Cancer Center (ethical number: 2301268-12) and was registered at China Clinical Trial Registry (registration number: ChiCTR2300069746).

Results:

A total of 1054 patients with UC were included. Most of the tumors were bladder UC (

=807

76.6%). The mean age of patients was (66.8±10.5) years

and the majority were male (78.5%). The HER2 overexpression rate was 58.4% (

=616)

with an additional 23% of patients having HER2 1＋ expression (

=242)

and a small proportion exhibiting negative HER2 expression (

=196

18.6%). HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group (ECOG) performance status

history of cardiovascular disease

history of metabolic disorders

smoking

UC disease location

differentiation grade

pathological type

and tumor stage.

Conclusion:

Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients

with an overexpression rate of up to 58.4%. Furthermore

HER2 expression is closely associated with various clinical and pathological features of UC patients. This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

关键词

Keywords

references

SORIA F , SHARIAT S F , LERNER S P , et al. Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC) [J ] . World J Urol , 2017 , 35 ( 3 ): 379 - 387 . DOI: 10.1007/s00345-016-1928-x http://doi.org/10.1007/s00345-016-1928-x

HE W , CHEN C H , LIN T X , et al. Epidemiology, treatments, and related biomarkers of locally advanced or metastatic urothelial carcinoma in Chinese population: a scoping review [J ] . Cancer Med , 2023 , 12 ( 14 ): 15384 - 15403 .

GUPTA S , ANDREEV-DRAKHLIN A , FAJARDO O , et al. Platinum ineligibility and survival outcomes in patients with advanced urothelial carcinoma receiving first-line treatment [J ] . J Natl Cancer Inst , 2024 , 116 ( 4 ): 547 - 554 .

ZINNALL U , WEYERER V , COMPÉRAT E , et al. Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype [J ] . Hum Pathol , 2018 , 80 : 55 - 64 . DOI: S0046-8177(18)30190-4 http://doi.org/S0046-8177(18)30190-4

YOROZU T , SATO S , KIMURA T , et al. HER2 status in molecular subtypes of urothelial carcinoma of the renal pelvis and ureter [J ] . Clin Genitourin Cancer , 2020 , 18 ( 4 ): e443 -e449.

WEN F , LIN T H , ZHANG P , et al. RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2-positive locally advanced muscle-invasive urothelial bladder cancer: a multi-center phase Ib/II study (HOPE-03) [J ] . Front Oncol , 2023 , 13 : 1233196 .

SHENG X N , YAN X Q , WANG L , et al. Open-label, multicenter, phase II study of RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with locally advanced or metastatic urothelial carcinoma [J ] . Clin Cancer Res , 2021 , 27 ( 1 ): 43 - 51 . DOI: 10.1158/1078-0432.CCR-20-2488 http://doi.org/10.1158/1078-0432.CCR-20-2488

张孟尼 , 龚静 , 陈雪芹 , 等 . 尿路上皮癌429例HER2表达情况及临床病理学分析 [J ] . 中华病理学杂志 , 2023 , 52 ( 3 ): 243 - 249 .

ZHANG M N , GONG J , CHEN X Q , et al. Expression of HER2 in 429 cases of urothelial carcinoma and clinicopathological analysis [J ] . Chin J Pathol , 2023 , 52 ( 3 ): 243 - 249 .

黎美仁 , 路名芝 , 郑美蓉 , 等 . HER2及CD44v6在膀胱尿路上皮癌中的表达及意义 [J ] . 中国老年学杂志 , 2018 , 38 ( 19 ): 4641 - 4647 .

LI M R , LU M Z , ZHENG M R , et al. Expression and significance of HER2 and CD44v6 in bladder urothelial carcinoma [J ] . Chin J Gerontol , 2018 , 38 ( 19 ): 4641 - 4647 .

中国抗癌协会肿瘤病理专业委员会 , 中国临床肿瘤学会尿路上皮癌专家委员会 . 中国尿路上皮癌人表皮生长因子受体2检测临床病理专家共识 [J ] . 中华肿瘤杂志 , 2021 , 43 ( 10 ): 1001 - 1006 .

Tumor Pathology Committee of Chinese Anti-Cancer Association, Expert Committee on Urothelial Carcinoma of Chinese Society of Clinical Oncology . Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China [J ] . Chin J Oncol , 2021 , 43 ( 10 ): 1001 - 1006 .

WANG J Y , LIU Y J , ZHANG Q Y , et al. RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with HER2-positive and HER2-low expressing advanced or metastatic breast cancer: a pooled analysis of two studies [J ] . J Clin Oncol , 2021 , 39 ( 15_suppl ): 1022 .

王磊 , 谢进东 . HER2在膀胱尿路上皮癌中的表达及意义 [J ] . 右江医学 , 2009 , 37 ( 4 ): 386 - 388 .

WANG L , XIE J D . The expression and significance of HER2 in uroepithelium cell carcinoma of bladder [J ] . Mod Chin Med , 2009 , 37 ( 4 ): 386 - 388 .

KHALIFA S E . Immunohistochemical expression of CD117/KIT, HER2, and Erβ in schistosomal and non-schistosomal urothelial carcinoma of Egyptian patients [J ] . Int Urol Nephrol , 2023 , 55 ( 10 ): 2473 - 2481 . DOI: 10.1007/s11255-023-03667-1 http://doi.org/10.1007/s11255-023-03667-1

SCHERRER E , KANG A , BLOUDEK L M , et al. HER2 expression in urothelial carcinoma, a systematic literature review [J ] . Front Oncol , 2022 , 12 : 1011885 .

黎美仁 , 郑美蓉 , 周燕 , 等 . 膀胱尿路上皮癌中HER2基因扩增及蛋白表达的意义 [J ] . 赣南医学院学报 , 2015 , 35 ( 4 ): 514 - 517 .

LI M R , ZHENG M R , ZHOU Y , et al. Gene amplification and protein expression of the human epidermal growth factor receptor 2 in urothelial carcinoma of bladder [J ] . J Gannan Med Univ , 2015 , 35 ( 4 ): 514 - 517 .

王婧婧 , 吴景 , 尹恬恬 , 等 . HER2与膀胱尿路上皮癌临床病理分子分型的相关性 [J ] . 中山大学学报(医学科学版) , 2020 , 41 ( 5 ): 758 - 766 .

WANG J J , WU J , YIN T T , et al. Correlation of HER2 with clinicopathologic features and molecular subtypes of urothelial bladder carcinoma [J ] . J Sun Yat Sen Univ Med Sci , 2020 , 41 ( 5 ): 758 - 766 .

管建云 , 李军扩 . HER2在膀胱尿路上皮细胞癌组织中的表达及其临床意义 [J ] . 中国当代医药 , 2014 , 21 ( 24 ): 13 - 15 .

GUAN J Y , LI J K . The expression and clinical significance of HER2 in bladder urothelial cell carcinoma [J ] . China Mod Med , 2014 , 21 ( 24 ): 13 - 15 .

ZHU K J , CHANG Y , ZHAO D L , et al. Expression of HER2 in high-grade urothelial carcinoma based on Chinese expert consensus and the clinical effects of disitamab vedotin-tislelizumab combination therapy in the treatment of advanced patients [J ] . Front Pharmacol , 2024 , 15 : 1355081 .

ZHOU L , SHAO Z T , LIU Y Q , et al. HER2 expression associated with clinical characteristics and prognosis of urothelial carcinoma in a Chinese population [J ] . Oncologist , 2023 , 28 ( 8 ): e617 -e624. DOI: 10.1093/oncolo/oyad070 http://doi.org/10.1093/oncolo/oyad070

LIN M X , LUO T , JIN Y Z , et al. HER2-low heterogeneity between primary and paired recurrent/metastatic breast cancer: Implications in treatment and prognosis [J ] . Cancer , 2024 , 130 ( 6 ): 851 - 862 .

ALMSTEDT K , KRAUTHAUSER L , KAPPENBERG F , et al. Discordance of HER2-low between primary tumors and matched distant metastases in breast cancer [J ] . Cancers , 2023 , 15 ( 5 ): 1413 .

浏览量

1634

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

荧光原位杂交与尿脱落细胞学在尿路上皮癌诊断中的效能比较：一项单中心回顾性队列研究

Circ-0007766作为miR-1972海绵调控HER2表达促进乳腺癌细胞迁移和侵袭

抗体药物偶联物在HER2阳性晚期胃癌中的应用进展和展望

HER2低表达乳腺癌新辅助化疗效果及其预后特征：一项单中心回顾性研究

人工智能辅助技术在胃癌新辅助化疗患者HER2表达评估中的价值