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

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高表达的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HER22+及3+定义为HER2高表达。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1054例UC患者,其中以膀胱UC为主(n=807,76.6%),平均年龄为(66.8±10.5)岁,多数(78.5%)患者为男性。HER2高表达率为58.4%(n=616),此外还有23%的患者为HER21+表达(n=242),少数(n=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HER2表达普遍存在,高表达率达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。

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug effi cacy 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 effi cacy 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:①age above 18 years;②UC diagnosed by histopathological or cytological examination;③complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:①diagnosed patients with tumors in other parts of the body;②physicians 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 HER22+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 University 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(n=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%(n=616),with an additional 23%of patients having HER21+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=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.