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Pyrotinib and chrysin synergistically potentiate autophagy in her2-positive breast cancer

Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu Jie Chen Ping He Yan Cheng Kunrui Zhu Dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(her2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new her2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in her2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against her2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in her2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： her2 synergistic Together

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SHR-A1811(antibody-drug conjugate)in advanced her2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin Liang Sheng Hu Min Peng Yan Yu Yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical Oncology Hubei Cancer HospitalWuhan 43000China Department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated her2-altered advanced non-small cell lung cancer(NSCLC).here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had her2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced her2-mutantNSCLC.

关键词： SHR her2 doses

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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant her2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China Department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(her2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of her2+ breast cancer. However, the efficacy of pyrotinib in her2+ breast cancer with primary trastuzumab resistance is ***: her2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and her2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive her2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and her2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and her2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant her2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in her2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and her2 downstream pathways in her2+ breast cancer with primary resistance

关键词： Breast cancer her2 pyrotinib trastuzumab primary resistance pertuzumab

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Association between Helicobacter pylori infection,mismatch repair,her2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(***)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively *** of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive *** To determine the rates of deficient mismatch-repair(dMMR),her2-status and *** infection and their association with TIL levels in *** Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)*** density of CD3,CD8 and CD163 immune cells,and dMMR and her2-status were determined by immunohistochemistry(IHC).*** infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of *** dMMR was found in 34.4%,her2+in 5%and ***-positive in 55.7%of *** IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P2-was associated with high IT-CD8(P=0.009).*** was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and *** CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori her2 Mismatch repair

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Mechanisms of resistance to trastuzumab in her2-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第3期36卷 306-321页

作者： Zhifei Li Huan Zhao Huihui Hu Haili Shang Yongjing Ren Wenhui Qiu Hao Su Huifang Lyu Xiaobing Chen Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Precision Therapy of Gastrointestinal CancerZhengzhou Key Laboratory for Precision Therapy of Gastrointestinal CancerZhengzhou 450008China Henan University of Traditional Chinese Medicine Zhengzhou 450046China State Key Laboratory of Esophageal Cancer Prevention&Treatment Key Laboratory of Advanced Drug Preparation TechnologiesMinistry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China The First Affiliated Hospital of Xinxiang Medical University Xinxiang 453000China Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China

Gastric cancer is one of the most prevalent cancers worldwide,and human epidermal growth factor receptor 2(her2)-positive cases account for approximately 20%of the total ***,trastuzumab+chemotherapy is the recommended first-line treatment for patients with her2-positive advanced gastric cancer,and the combination has exhibited definite efficacy in her2-targeted ***,the emergence of drug resistance during treatment considerably reduces its effectiveness;thus,it is imperative to investigate the potential mechanisms underlying *** the present review article,we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in her2-positive gastric cancer cases,aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

关键词： her2 gastric cancer trastuzumab drug resistance

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Assessment of her2 status in extramammary Paget disease and its implication for disitamab vedotin,a novel humanized anti-her2 antibody-drug conjugate therapy

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Frontiers of Medicine 2024年第3期18卷 565-569页

作者： Jia Jia Lili Mao Jing Lin Wenyu Li Pei Yuan Lei Guo Jie Dai Caili Li Xue Bai Zhongwu Li Yu Chen Jun Guo Jianming Ying Lu Si State Key Laboratory of Molecular Oncology Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Melanoma and SarcomaPeking University Cancer Hospital&InstituteBeijing100142China Department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou350014China Department of Pathology Peking University Cancer Hospital&InstituteBeijing100142China

Dear Editor,Extramammary Paget disease(EMPD)is a rare adenocarcinoma that originates in the apocrine gland-rich skin and usually affects the perineal skin(primary EMPD)or represents the intraepithelial spread of an underlying visceral carcinoma(secondary EMPD).Approximately half of EMPD cases are confined to the epidermis,which was defined as intraepithelial EMPD.

关键词： Paget her2 adenocarcinoma

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基于超声图像的肿瘤亚区域特征评估浸润性乳腺癌her2表达异质性的价值

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中国超声医学杂志 2024年第7期40卷 749-752页

作者：吴林永魏达友林艳李松桦何敏诗茂名市人民医院超声医学科茂名市人民医院病理科

目的探讨基于超声图像的肿瘤亚区域特征评估浸润性乳腺癌(IBC)人表皮生长因子受体2(her2)瘤内表达异质性的价值。方法回顾性分析90例her2阳性和39例her2阴性表达IBC患者的超声临床资料，并分为训练(n=90)和验证(n=39)队列。采用K均值... 详细信息

目的探讨基于超声图像的肿瘤亚区域特征评估浸润性乳腺癌(IBC)人表皮生长因子受体2(her2)瘤内表达异质性的价值。方法回顾性分析90例her2阳性和39例her2阴性表达IBC患者的超声临床资料，并分为训练(n=90)和验证(n=39)队列。采用K均值共识别聚类方法将肿瘤整体区域划分为不同肿瘤亚区域，提取整体和亚区域特征。特征选择采用最小绝对收缩和选择算子方法，并提交给光梯度提升机(Light GBM)和梯度增强机器学习算法开发评估IBC-her2阳性表达模型。使用受试者工作特性曲线下面积(AUC)评估模型效果。结果基于肿瘤整体区域划分为A和B两个肿瘤亚区域。基于亚区域特征的机器学习模型均优于基于肿瘤整体区域特征，特别是B亚区域，Light GBM模型在训练和验证队列中表现最优，AUC分别为0.87和0.92,准确度分别为81%和85%。结论本研究揭示了基于超声图像的肿瘤亚区域特征相对于肿瘤整体区域特征可更好地解析IBC-her2表达的瘤内异质性，具有潜在实现非侵入性成像特征表征肿瘤分子异质性，达到精准诊疗目标的价值。

关键词：浸润性乳腺癌异质性 her2 肿瘤亚区域超声

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基于双模态乳腺影像特征的her2表达状态多分类机器学习预测模型构建及可解释性分析研究

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临床放射学杂志 2024年第8期43卷 1310-1316页

作者：舒予静何子龙曾伟雄刘家玲郭丫丫陈卫国南方医科大学南方医院放射科广州510515 广东医科大学附属东莞第一医院放射影像中心东莞523710

目的基于乳腺X线及超声双模态影像特征构建多分类机器学习模型,术前预测乳腺癌患者的人类表皮生长因子受体2(her2)表达状态。方法搜集符合纳排标准的632例女性乳腺癌患者,其中her2不表达141例、低表达311例、高表达180例。提取研究对象... 详细信息

目的基于乳腺X线及超声双模态影像特征构建多分类机器学习模型,术前预测乳腺癌患者的人类表皮生长因子受体2(her2)表达状态。方法搜集符合纳排标准的632例女性乳腺癌患者,其中her2不表达141例、低表达311例、高表达180例。提取研究对象全视野数字化乳腺X线摄影(FFDM)、数字乳腺断层摄影(DBT)以及乳腺超声(US)图像上乳腺癌病灶的影像学征象。在完成数据预处理后,基于五种机器学习算法构建乳腺癌her2表达状态的三分类预测模型。采用五折交叉验证训练机器学习模型,计算三分类模型的总体准确率、精确率、查全率、F1⁃score、受试者工作特征曲线(ROC)曲线下面积(AUC)值。通过Bootstrap法比较模型间AUC值,筛选出分类性能最优的三分类模型。采用SHAP方法评估每个特征对模型预测her2表达状态的重要性。结果在测试集上,随机森林(RF)模型对her2表达状态的三分类性能最优,宏平均AUC为0.723,微平均AUC为0.783,总体准确率为57.4%,宏平均召回率为53.0%。SHAP分析结果表明,影响RF模型输出最重要的五个全局特征依次为X线观察到的钙化、舒张压、细线样或线样分支状钙化、US测量的病灶最大径、CA153。结论基于乳腺X线及超声双模态影像特征的机器学习多分类模型可以实现乳腺癌患者her2表达状态的术前预测,结合SHAP方法可以提高机器学习模型的可解释性。

关键词：乳腺癌 her2 表达状态乳腺X 线摄影超声机器学习

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HR阳性乳腺癌新辅助治疗后her2阴性亚组蛋白水平表达的演变及与临床病理特征的相关性分析

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临床与实验病理学杂志 2024年第9期40卷 955-960,966页

作者：孙雪梅苗佳贤卜维航郭启涛刘月平河北医科大学第四医院病理科石家庄050011

目的探讨激素受体(hormone receptor, HR)阳性、her2阴性亚组[极低表达(Ultra-low)和完全无表达(Null)]乳腺癌新辅助治疗前后的演变及其与临床病理特征的关系。方法回顾性分析术前接受新辅助治疗且治疗后未达到病理完全缓解(pathologi... 详细信息

目的探讨激素受体(hormone receptor, HR)阳性、her2阴性亚组[极低表达(Ultra-low)和完全无表达(Null)]乳腺癌新辅助治疗前后的演变及其与临床病理特征的关系。方法回顾性分析术前接受新辅助治疗且治疗后未达到病理完全缓解(pathological complete response, pCR)的连续性乳腺癌病例255例,采用免疫组化法检测ER、PR、her2和Ki67的表达情况,并评价her2阴性亚组表达水平新辅助治疗后的演变及与乳腺癌临床病理特征的关系。结果 255例乳腺癌患者中新辅助治疗前her2-0和her2-1+的例数分别为116例(45.5%)和139例(54.5%),her2-0进一步划分为Null 61例(23.9%)和Ultra-low 55例(21.6%)。新辅助治疗后her2-0和her2-1+例数分别为117例(45.9%)和138例(54.1%),her2-0进一步划分为Null 64例(25.1%)和Ultra-low 53例(20.8%)。新辅助治疗后有121例(47.5%)患者her2表达水平发生了转变,其中,新辅助治疗前为her2 Ultra-low,治疗后转变为1+,转变率最高,为11.76%(30/255),其次为1+转变为Ultra-low,转变率为10.98%(28/255);新辅助治疗后,her2 Ultra-low组55例中44例发生了转变,其转变率高达80%。χ^(2)检验显示新辅助治疗前her2表达与新辅助治疗后肿瘤最大径(≤2 cm,>2 cm)有关(χ^(2)=6.106,P=0.047),治疗前her2 1+的患者治疗后肿瘤最大径≤2 cm居多;新辅助治疗后her2表达与新辅助治疗后脉管瘤栓有关(χ^(2)=6.975,P=0.029),治疗后her2 Ultra-low患者更容易出现脉管瘤栓。结论 HR阳性的乳腺癌中,对her2-0重新划分为Ultra-low和Null后,新辅助治疗后her2转变率明显增高,并且Ultra-low转变率最高,说明Ultra-low病例在新辅助治疗后具有高度不稳定性,对于新辅助治疗后残余病灶her2的检测并区分Ultra-low的表达十分重要。

关键词：乳腺肿瘤 her2 极低表达新辅助治疗激素受体

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膀胱尿路上皮癌her2表达及临床病理分析

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临床与实验病理学杂志 2024年第4期40卷 380-385页

作者：尹玉仲坤李雪罗文武蒋俊兰安徽医科大学第一附属医院病理科合肥230022 安徽医科大学基础医学院病理学教研室合肥230032 安徽理工大学第一附属医院病理科淮南232007

目的探讨膀胱尿路上皮癌(bladder urothelial carcinoma,BUC)中her2的表达情况,并分析其临床意义。方法收集膀胱非浸润性低级别BUC 27例、非浸润性高级别BUC 5例、浸润性高级别BUC 60例,采用免疫组化MaxVision法法检测各组织样本中her2... 详细信息

目的探讨膀胱尿路上皮癌(bladder urothelial carcinoma,BUC)中her2的表达情况,并分析其临床意义。方法收集膀胱非浸润性低级别BUC 27例、非浸润性高级别BUC 5例、浸润性高级别BUC 60例,采用免疫组化MaxVision法法检测各组织样本中her2蛋白的表达,并分析her2表达与临床病理特征的关系。通过GEPIA数据库或直接在肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)中分析her2(ERBB2)表达与BUC的关系。结果浸润性高级别BUC中her22+/3+表达率(26.67%,16/60)显著高于非浸润性低级别BUC(7.41%,2/27)和非浸润性高级别BUC(0,0/5)(Pher22+/3+表达率(75.00%,6/8)显著高于单灶性患者(19.23%,10/52)(Pher22+/3+表达率差异有统计学意义(P20)、腺样分化型为57.14%(4/7)、微乳头型为66.67%(4/6)、浆细胞样型为100.00%(2/2),余亚型均为0/1+。her2表达与其他临床病理特征均无明显相关性(P>0.05)。GEPIA数据库中,BUC肿瘤组织中her2(ERBB2)表达高于正常组织(P>0.05),her2(ERBB2)高表达患者的总生存期(overall survival,OS)低于her2(ERBB2)低表达(P>0.05);对TCGA数据进行Cox单因素分析显示:年龄、分期、T和N越高的患者OS较短。结论浸润性高级别BUC中her22+/3+表达率高于非浸润性低级别和高级别BUC,并与肿瘤个数、组织学亚型密切相关,提示结合her2表达状态、肿瘤个数和组织学亚型或有助于筛选出可能从her2靶向治疗中获益的浸润性高级别BUC患者。

关键词：膀胱尿路上皮癌浸润性高级别尿路上皮癌 her2 临床病理免疫组织化学

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