双色荧光原位杂交技术在膀胱尿路上皮肿瘤诊断中的应用价值

 目的 探讨双色荧光原位杂交技术（FISH)诊断膀胱尿路上皮肿瘤的临床应用价值。方法 标记为3,7,17号染色体着丝粒及9号染色体p16位点9p21区带探针,采用FISH对80例膀胱尿路上皮肿瘤患者尿液间期细胞核进行荧光原位杂交,同时选取20例健康体检者作为正常对照组,建立阈值,以组织病理结果作为诊断“金标准”,统计染色体畸变情况,分析其与病理分期、分级的关系以及染色体畸变组合诊断膀胱尿路上皮肿瘤的敏感性。结果 3、7、17号染色体和9p21的畸变率分别为47.5%（38/80）、60.7%（49/80）、51.3%（41/80）和58.8%（47/80）,3、7、9和17号染色体联合检测膀胱癌的阳性率为76.3%(61/80),畸变和肿瘤分期无相关性,3、7、17号染色体与肿瘤病理分级有显著相关性（P﹤0.05）。 结论 膀胱尿路上皮肿瘤的进展可能与染色体的畸变有关,FISH可以作为膀胱尿路上皮肿瘤诊断的一项重要方法,并可能在术后监测复发以及预后判断中具有重要临床意义。     

多色荧光原位杂交在膀胱尿路I皮癌诊断中的应用

背景与目的:膀胱尿路上皮癌是我国泌尿生殖系统常见的恶性肿瘤.本研究旨在分析中国人膀胱尿路上皮癌中染色体畸变的情况,探讨多色荧光原位杂交(multicolor fluorescence in situ hybridization,M-FISH)技术辅助诊断膀胱尿路上皮癌的可行性和有效性.方法:用随机引物法标记3、7、17号染色体着丝粒及9p21区带探针,对57例膀胱尿路上皮癌间期细胞核进行荧光原位杂交(fluorescence in situ hybridization,FISH),统计染色体畸变情况并分析其与病理分期、分级的关系以及染色体畸变组合诊断膀胱尿路上皮癌的阳性率.结果:3、7、17号染色体和9p21的畸变率分别为47.4%(27/57)、50.9%(29/57)、56.1%(32/57)和59.6%(34/57),畸变与分期无相关性,3、7和17号染色体畸变与病理分级有显著相关性(P＜0.01).四个探针组合诊断膀胱尿路上皮癌的总阳性率为54.4%.结论:M-FISH技术检测有助于探索3、7、17号染色体畸变与病理分级的关系.     

膀胱癌荧光原位杂交检测及其临床意义

目的:分析膀胱移行细胞癌的染色体畸变情况,探讨荧光原位杂交(FISH)技术在膀胱癌的临床应用价值.方法:采用3、7、17号染色体着丝粒探针和9号染色体p16基因位点探针对56例膀胱移行细胞癌患者和20名健康人群的新鲜尿液进行FISH检测,统计染色体的畸变并分析其与病理分级、分期的关系.对所有病例同步进行尿细胞学分析.结果:膀胱癌患者尿脱落细胞核中3、7、17号染色体及9号染色体p16基因畸变率分别为58.9%、39.3%、58.9%和75.0%,各染色体畸变在膀胱癌不同分期之间的差异无统计学意义(P>0.05),3、7、17号染色体畸变在不同分级之间的差异具有统计学意义(P<0.05),四染色体探针组合诊断膀胱癌的总阳性率为80.4%;膀胱癌尿脱落细胞的FISH检出率明显高于尿细胞形态学.结论:膀胱癌的发生发展与染色体的畸变有关,膀胱癌尿脱落细胞的FISH检测,对膀胱癌的早期诊断、预后评估及复发监测等具有重要价值.     

荧光原位杂交技术在膀胱尿路上皮肿瘤病理学诊断中的初步应用

目的应用荧光原位杂交（fluorescence in situ hybridization,FISH）技术,了解膀胱尿路上皮肿瘤细胞核染色体畸变情况及其对病理诊断及鉴别诊断的应用价值。方法采用3、7、17号染色体着丝粒及p16基因探针,对33例不同级别膀胱尿路上皮肿瘤组织和10例正常对照膀胱组织进行FISH检测。结果 3、7、17染色体及p16扩增率与缺失率,浸润性尿路上皮癌与其他5组比较均有统计学意义（P〈0.01）;而其他各组间比较无统计学意义（P〉0.05）,4种探针联合检测≥2个指标出现异常,浸润性尿路上皮癌占100%,与其他5组比较有统计学意义（P〈0.01）;该指标对浸润性尿路上皮癌诊断敏感性为81.82%、特异性为91.67%。结论应用FISH技术,可以了解膀胱尿路上皮肿瘤组织3、7、17染色体及p16基因的畸变情况,FISH技术还可作为尿路上皮肿瘤病理学诊断与鉴别诊断及术后监测的重要手段。     

荧光原位杂交检测尿路上皮癌分子细胞遗传学变异的临床应用研究*

目的:探讨荧光原位杂交（fluorescence in situ hybridization,FISH）在检测尿路上皮癌患者尿液中脱落细胞核染色体畸变的临床应用价值。方法:采用3 号、7 号及17号染色体着丝粒特异性探针及p16位点特异性DNA探针对20例正常人尿液进行FISH检测,建立阈值。对115 例疑似尿路上皮肿瘤血尿患者的尿液进行FISH检测,以至少两种探针检测结果超过阈值或一种探针检测结果存在至少两种异常为诊断阳性。同时采用常规HE染色法进行尿脱落细胞形态学分析。结果:荧光原位杂交（FISH）技术和尿脱落细胞学诊断尿路上皮癌的灵敏度分别为86.7%（78/90）和10.0%（9/90）（P<0.001）;特异度分别为96.0%（24/25）和100%（25/25）（P>0.05）;阳性预测值分别为98.7%（78/79）和100%（9/9）（P>0.05）;阴性预测值分别为66.7%（24/36）和23.6%（25/106）（P<0.05）。 FISH技术诊断尿路上皮癌的灵敏度与尿路上皮癌的病理分级及分期无关,低级别和高级别尿路上皮癌FISH技术诊断的阳性率分别为85.7% 和87.5%（P>0.05）;非肌层浸润性和肌层浸润性尿路上皮癌的阳性率分别为84.2% 和88.4%（P>0.05）。 结论:尿脱落细胞荧光原位杂交技术诊断尿路上皮癌灵敏度高,特异度强,无创伤性,可作为尿路上皮癌早期诊断的一项重要方法,并可在预测肿瘤生物学行为及预后关系上具有重要的临床意义。      

应用荧光原位杂交技术诊断尿路上皮癌的临床研究

背景与目的：尿路上皮癌是一种最常见的泌尿系统肿瘤,尿细胞学检查是诊断尿路上皮癌的经典方法,虽然特异度较高,但是敏感度偏低。目前荧光原位杂交技术（fluorescence in situ hybridization,FISH）计数分裂间期细胞的染色体倍数已成功应用于遗传学和肿瘤学研究领域。本研究旨在评价FISH在诊断尿路上皮癌中的诊断价值。方法：采用FISH检测100例血尿患者尿脱落细胞中3、7、9和17号染色体数目异常,以组织病理确诊为尿路上皮癌为金标准,评估FISH诊断的特异度和敏感度,并与尿细胞学检查结果做比较。结果：FISH诊断尿路上皮癌特异度为92.3%,敏感度为74.7%;尿细胞学诊断特异度为100%,敏感度为46.0%。两者相比,敏感度差异有统计学意义（P〈0.05）,而特异度差异无统计学意义（P〉0.05）。结论：与尿细胞学相比,FISH诊断尿路上皮癌具有较高的特异度和相似的特异度敏感度,可作为诊断尿路上皮癌的新方法。     

荧光原位杂交在尿路上皮癌诊断中的应用

目的:检测尿路上皮肿瘤患者尿液脱落细胞染色体的缺失和非整倍异常,探讨FISH技术作为尿路上皮肿瘤患者无创诊断方法的价值.方法:收集可疑尿路上皮肿瘤患者和健康对照人群的新鲜尿液,同步进行细胞形态学分析及荧光原位杂交(Fluorescencein situ hybridization,FISH)检测3号、7号及17号染色体、9号染色体p16位点异常.共入选可疑尿路上皮肿瘤患者100例,正常健康对照组20例,采用正常对照组患者各染色体异常数据设定阈值用于肿瘤患者的实验室诊断.根据检验结果与病理结果对照分别计算FISH和脱落细胞的敏感度和特异度并进行统计学分析.结果:与正常对照组相比,尿路上皮肿瘤患者尿液脱落细胞染色体异常明显增多.尿脱落细胞学的敏感度和特异度分别为71%和80%,FISH的敏感度和特异度分别为88%和80%(P<0.01).根据两种检测方法的敏感度和特异度绘制的接受者工作特征(ROC)曲线显示尿脱落细胞学和FISH的曲线下面积分别为0.758和0.842.结论:对可疑尿路上皮肿瘤的患者进行FISH检测是一种有价值的无创检测方法.FISH的总体敏感度高于尿脱落细胞学,特异度与尿脱落细胞学相当.     

膀胱移行细胞癌的分子细胞遗传学研究

目的　分析膀胱移行细胞癌的染色体畸变。方法　采用 7,9,11,17号染色体着丝粒探针对 34例膀胱移行细胞癌患者尿液、30例膀胱冲洗液的脱落细胞核进行荧光原位杂交 (fluorescenceinsituhybridization ,FISH )研究 ,并同时做了细胞学检查。结果　 (1)膀胱癌患者尿液脱落细胞核中 7,9,11,17号染色体数目畸变阳性率分别为 2 3.5 %、38.2 %、14.7%和 11.8% ;冲洗液中各号染色体畸变阳性率分别为 30 .0 %、5 0 .0 %、2 6 .7%和 16 .7%。其中 9号染色体畸变率较高 ,但与膀胱癌分级、分期无明显关系 ;7号染色体数目畸变与膀胱癌的分期密切相关 ;11,17号染色体数目畸变与膀胱癌分级、分期无显著相关性。 (2 )膀胱癌患者尿液组中尿细胞学、FISH阳性率分别为 2 9.4%和 5 5 .9% ,两种方法联合后阳性率达 6 7.6 % ;膀胱冲洗液组中阳性率则分别为 2 7.6 %和 73.7% ,两种方法联合后阳性率达 80 .0 %。结论　膀胱癌的发生发展与染色体的畸变有关。FISH检测膀胱癌患者尿液、冲洗液脱落细胞间期核染色体数目畸变 ,有可能作为膀胱癌诊断、预后判断的一项辅助方法。     

应用荧光原位杂交技术检测膀胱癌的研究

目的应用荧光原位杂交((fluorescence in situ hybridization,FISH)技术检测膀胱癌患者尿液脱落细胞中染色体异常,评估FISH在中国人群中诊断膀胱癌的作用。方法2007年1月至2008年8月,随机留取20例良性前列腺增生症患者的新鲜尿液,用3号和7号、17号及p16位两组混合探针,通过在尿液脱落细胞标本上进行FISH检测,建立正常人群的阈值;其后随机留取30例门诊膀胱镜活检证实的膀胱癌患者的尿液,同时进行尿液脱落细胞的细胞形态学分析及FISH检测,对比检查结果。结果3号、7号和17号染色体非整倍性改变及p16位点异常正常阈值分别为8.5%、7.1%、6.8%和9.2%,FISH与细胞学检查总敏感性分别为76.6%和43.3%(P<0.05)。T_(is)及T_a、T_1患者FISH检测的敏感性分别为80.0%和64.2%,脱落细胞组织学检测显示敏感性分别为40.0%和35.7%;T_(2-3)患者FISH的敏感性为90.9%,而脱落细胞组织学检测为54.7%(P<0.05),低级别尿路上皮癌FISH及细胞学敏感性分别为68.4%和31.6%;高级别分别为90.9%和63.6%。结论与尿液脱落细胞组织学检测相比,对尿液脱落细胞进行FISH检测可以提高膀胱癌的诊断率,FISH可以作为诊断膀胱癌的一种无创伤的新方法。     

尿脱落细胞Lewis X检测诊断膀胱尿路上皮癌的价值

目的探讨Lewis X抗原在膀胱尿路上皮癌非侵袭性诊断中的应用价值.方法采用EnVision免疫细胞化学方法,检测52例膀胱尿路上皮癌和16例非肿瘤患者尿脱落细胞标本中Lewis X抗原的表达情况,并与细胞病理学检测结果相比较.结果尿路上皮癌诊断的敏感性和特异性分别为84.6%和87.5%,其敏感性显著高于细胞病理学.结论尿脱落细胞Lewis X抗原免疫染色,是检测膀胱尿路上皮癌可行的较敏感的非侵袭性方法.     

Urothelial papilloma of the bladder. Clinical and biologic implications

BACKGROUND: An international consensus has been reached regarding diagnostic criteria for papilloma of the urinary bladder. However, the incidences of recurrence and progression in patients with urothelial papilloma are uncertain. METHODS: The population for this study consisted of 52 patients who were diagnosed with urothelial papilloma of the bladder at the Mayo Clinic between 1914 and 1998. All histologic slides were reviewed and fulfilled the diagnostic criteria of urothelial papilloma from the 1998 World Health Organization/International Society of Urological Pathology classification system. No patients had previous or coexistent urothelial carcinoma, and none were treated after biopsy. RESULTS: The mean patient age at diagnosis was 57 years (range, 22-89 years). The male-to-female ratio was 1.9:1. The mean follow-up was 9.8 years (range, 0.1-58 years). Four patients developed recurrent papilloma (mean interval from diagnosis to recurrence, 3.3 years); 1 other patient developed papillary neoplasm of low malignant potential (Ta WHO Grade 1 papillary urothelial carcinoma) 6 years after the initial diagnosis of papilloma. None of these patients developed dysplasia, carcinoma in situ, or invasive urothelial carcinoma or died of bladder cancer. CONCLUSIONS: Patients with urothelial papilloma have a low incidence of recurrence and rarely, if ever, develop urothelial carcinoma.     

Examination of Diagnostic Accuracy of UroVysion Fluorescence In Situ Hybridization for Bladder Cancer in a Single Community of Japanese Hospital Patients

Objective: UroVysion (Abbott Molecular, Inc., Illinois, USA) is based on multicolor fluorescence in situ hybridization(FISH). It has been used successfully in the USA following its Food and Drug Administration approval in 2001. However,the technology was not approved for use in Japan until 2017. Cystoscopy and urine cytology are the most frequentlyused examinations to detect bladder cancer in Japan, and there are only a few reports regarding the performance ofUroVysion. Therefore, the aim of this study is to examine the diagnostic accuracy of UroVysion FISH in Japanesepatients whose tumors are detected by cystoscopy before transurethral resection of bladder tumor (TURBT). Methods:From April 2018 to July 2018, a total of 40 patients who were diagnosed as having bladder tumors by cystoscopy, andtherefore underwent TURBT were registered in this study. One day before TURBT, urine cytology and UroVysionFISH were used in order to compare the accuracy with which they could detect bladder carcinoma, as confirmed bypathological results of TURBT. Results: The pathological results of TURBT showed urothelial carcinoma in 33 cases.Urine cytology showed positive results for 0 cases (0%), suspicious results for 10 cases (30.3%), and negative resultsfor 23 cases (69.7%). On the other hand, UroVysion FISH indicated 9 positive cases (27.3%) and 24 negative cases(72.7%). There were 19 cases of urothelial carcinoma (57.6%) that were not detected by either method. Conclusion:We conclude that UroVysion FISH alone is insufficient to detect bladder cancer and that cystoscopy is essential for theoptimum detection or follow up of bladder cancer cases in our hospital.     

Papillary urothelial neoplasms of low malignant potential. Clinical and biologic implications

BACKGROUND: Knowledge of the long term outcomes of patients with papillary urothelial neoplasms of low malignant potential (LMP) is limited. METHODS: The authors studied 112 consecutive patients who were diagnosed with papillary urothelial neoplasms of LMP (formerly Ta, World Health Organization Grade 1 of 3 papillary urothelial carcinoma) at the Mayo Clinic between 1958 and 1963. All histologic slides were reviewed and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. RESULTS: Patient age at diagnosis ranged from 33 to 99 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 12.8 years (range, 0.1-35 years; median, 11.7 years). Twelve patients had biopsy-proven, noninvasive urothelial carcinoma; 17 patients had cystoscopically detected recurrences (all were treated by fulguration without biopsy); and 4 patients developed invasive urothelial carcinoma (including 2 with muscle-invasive carcinoma). Twelve (75%) of 16 patients with biopsy-proven recurrence or progression had cancer dedifferentiation, which resulted in a diagnosis of higher grade cancer than was indicated on initial biopsies. The mean interval from initial diagnosis to development of invasive carcinoma was 13.3 years (range, 10-14 years). Three patients died of bladder cancer. CONCLUSIONS: Patients with papillary urothelial neoplasms of LMP have increased risks of local recurrence, progression, and death from bladder carcinoma. Long term clinical follow-up may be indicated for patient management.     

NUSAP1在膀胱尿路上皮癌中的表达及对预后评估的价值

目的:检测核仁和纺锤体相关蛋白1(NUSAP1)在膀胱尿路上皮癌中的表达及对预后评估的价值。方法:采用免疫组化方法检测NUSAP1在84例膀胱尿路上皮癌组织及10例正常膀胱上皮组织中的表达情况，并分析其表达与临床病理特征的关系；采用Western blot检测NUSAP1蛋白在T24和SV-HUC-1细胞系中的表达；采用单因素和多因素COX回归分析评价NUSAP1在膀胱尿路上皮癌中的预后价值。结果:免疫组织化学结果显示NUSAP1在膀胱尿路上皮癌中的阳性表达率为72.62%，在正常膀胱上皮组织中的阳性表达率为10.00%，差异有统计学意义（P<0.05）。NUSAP1在膀胱尿路上皮癌中的高表达与患者性别、年龄、肿瘤数目均无关(P>0.05)，而与肿瘤复发、病理分级、临床分期、转移有关(P<0.05)。NUSAP1蛋白在T24细胞系中的表达明显高于SV-HUC-1细胞系，差异有统计学意义(P<0.05)。NUSAP1表达、临床分期和转移均为膀胱尿路上皮癌的独立预测因素。此外，Kaplan-Meier曲线表明，NUSAP1阳性表达的膀胱尿路上皮癌患者无进展生存时间（PFS）明显少于NUSAP1阴性表达者。结论:NUSAP1在膀胱尿路上皮癌中呈现高表达，且与肿瘤复发、病理分级、临床分期、转移有关，NUSAP1是膀胱尿路上皮癌独立危险因素，其高表达提示预后较差，具有一定的临床价值。     

Combined morphologic and fluorescence in situ hybridization analysis of voided urine samples for the detection and follow‐up of bladder cancer in patients with benign urine cytology

BACKGROUND.

Bladder cancer is among the 5 most common malignancies worldwide. Patients with bladder cancer are closely followed with periodic cystoscopies and urine cytology analyses due to the significant risk of tumor recurrence. The UroVysion fluorescence in situ hybridization (FISH) test demonstrated higher sensitivity over urine cytology in detecting bladder cancer by most comparative studies.

METHODS.

In the current study, the diagnostic usefulness of a combined cytology and FISH analysis approach was tested using the Duet automatic scanning system in patients with benign urine cytology who were being monitored for recurrent urothelial carcinoma or being assessed for various urologic symptoms.

RESULTS.

By combining the benefits of conventional cytology with molecular diagnostics, a more sensitive detection of bladder cancer was attained. All patients who had positive cystoscopy concomitantly with urine sampling were detected by combined analysis. Additional patients that developed transitional cell carcinoma during a follow‐up period of 24 months had a previous positive result on combined analysis. Only 2 patients with a negative combined analysis result presented with late disease recurrence (20 months and 22 months, respectively, after the negative test). Therefore, negative combined analysis was found to be predictive of a lack of disease recurrence for at least 12 months. In this timeframe, the overall sensitivity, specificity, negative predictive value (NPV), and positive predictive values of the combined analysis test were 100%, 65%, 100%, and 44%, respectively.

CONCLUSIONS.

Given the absolute sensitivity and NPV of the combined analysis test, the management of patients with a negative combined analysis result might be revised and allow for more flexible assessment and management of bladder cancer patients relying more on urine bound tests. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

MEK5在膀胱尿路上皮癌组织中的表达及预后相关性分析北大核心

目的:探究膀胱尿路上皮癌组织中丝裂原活化蛋白激酶5(mitogen-activated protein kinase 5,MEK5)表达水平及其与预后相关性。方法:选取2015年06月至2017年06月本院收治的膀胱尿路上皮癌患者93例作为研究对象,术中收集入组患者癌组织及癌旁组织。采用qRT-PCR法、免疫组化染色法检测膀胱尿路上皮癌组织及癌旁组织中MEK5表达;Kaplan-Meier法绘制生存曲线分析膀胱尿路上皮癌组织中MEK5表达与患者预后相关性;Cox比例风险回归模型分析影响膀胱尿路上皮癌患者不良预后发生的危险因素;受试者工作特征(ROC)曲线分析膀胱尿路上皮癌组织中MEK5 mRNA对患者预后不良预测价值。结果:膀胱尿路上皮癌组织中MEK5 mRNA表达水平及MEK5蛋白阳性率明显高于癌旁组织(P<0.05)。高级别、T_(2)-T_(4) TNM分期、浸润性及淋巴结转移膀胱尿路上皮癌患者癌组织中MEK5蛋白高表达率明显高于低级别、T_(a)-T_(1) TNM分期、非浸润性及无淋巴结转移患者(P<0.05)。MEK5蛋白高表达患者中无复发生存16例,无复发生存率为31.37%;MEK5蛋白低表达患者中无复发生存28例,无复发生存率为66.67%,两组比较差异有统计学意义(P<0.05)。浸润性、低级别、T_(2)-T_(4) TNM分期、淋巴结转移、MEK5高表达是影响膀胱尿路上皮癌患者不良预后发生的独立危险因素(P<0.05)。结论:膀胱尿路上皮癌组织中MEK5呈高表达,与患者TNM分期、病理分型、病理分级、淋巴结转移等密切相关,可能作为临床评估患者预后的参考指标。     

Multi-target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer

The objective of this study was to evaluate the diagnostic value of chromosomal analysis by fluorescence in situ hybridization (FISH) for predicting recurrence of urothelial carcinoma (UC) after transurethral resection. One hundred and thirty-eight patients (median age 68.5 years) with a history of UC were eligible for this prospective study. FISH was applied to cytospin specimens prepared from bladder washings taken during a negative control cystoscopy. The multi-target FISH test UroVysion (Abbott/Vysis) containing probes to the centromeres of chromosomes 3, 7, 17 and the 9p21 locus was used. UC recurrence was defined as a positive biopsy during follow-up. The median follow-up time was 19.2 (4-52) months. FISH was positive in 50 (36%) patients and negative in 88 (64%) patients. A recurrence occurred in 39% of the patients with a positive FISH test and in 21% of patients with a negative FISH test. FISH positivity according to manufacturer's criteria, at the time of a negative cystoscopy, was not significantly associated with the risk of recurrence (p = 0.12). However, the sensitivity of the FISH test to predict recurrence was significantly improved by considering specimens with rare (< or =10) tetraploid cells as negative (p < 0.006). In addition, presence of 9p21 deletion was significantly associated with recurrence (p < 0.01). Notably, positive standard cytology was an independent factor for subsequent recurrence in this study (p < 0.001). Taken together, multi-target FISH may help to stratify the risk of recurrence of UC at the time of a negative follow-up cystoscopy. Defining the optimal threshold for FISH positivity requires consideration of tetraploid pattern and 9p21 deletion. Our results also emphasize the paramount importance of conventional cytology for UC surveillance.     

Discussion on the influence of HER2 status on the clinical outcome of bladder cancer continues

Evaluation of: Bolenz C, Shariat SF, Karakiewicz PI et al. Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJUI 106, 1216-1222 (2010). The article under evaluation by Bolenz et al. reports on an association between human EGF receptor 2 (HER2) overexpression and aggressive urothelial carcinoma of the urinary bladder: more lymphovascular invasion, higher risk of recurrence and higher disease-specific mortality. These results add to the controversy regarding HER2 status and clinical outcome that is currently known. First, a consensus for the best technique and cut-off is needed. Only then can the relationship between HER2 overexpression and clinical outcome be investigated without current limitations. Although there are already trials ongoing on targeted therapy in bladder cancer, this should be viewed with caution, as patient selection is based on inconsistent definitions of HER2 overexpression. Selection of patients who might benefit from targeted therapy can only be carried out after consensus has been reached.