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Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population☆(☆ Hospitals 1 and 3w53 were all in the study group of Fluorescence in situ hybridization in prenatal genetic diseases and cancer detection in clinical research of Chinese population.) |
Liqun Zhoua,b,c,*(),Kaiwei Yanga,b,c,Xuesong Lia,b,c,Yi Dinga,b,c,Dawei Mud,Hanzhong Lie,Yong Yanf,Jinyi Lig,Dongwen Wangh,Wei Lii,Yulong Congj,Jiangping Gaoj,Kewei Mak,Yajun Xiaol,Sheng Zhangm,Hongyi Jiangn,Weilie Huo,Qiang Weip,Xunbo Jinq,Zhichen Guanr,Qingyong Lius,Danfeng Xut,Xin Gaou,Yongguang Jiangv,Weimin Ganw,Guang Sunx,Qing Wangy,Yanhui Liuz,Jianquan Houaa,Liping Xieab,Xishuang Songac,Fengshuo Jinad,Jiafu Fengae,Ming Caiaf,Zhaozhao Liangag,Jie Zhangah,Dingwei Yeai,Lin Qiaj,Lulin Maak,Jianzhong Shoual,Yuping Daiam,Jianyong Shaoan,Ye Tianao,Shizhe Hongap,Tao Xuaq,Chuize Kongar,Zefeng Kangas,Yuexin Liuat,Xun Quau,Benkang Shiau,Shaobin Zhengav,Yi Linaw,Shujie Xiaax,Dong Weiay,Jianbo Wuaz,Weiling Fuba,Zhiping Wangbb,Jianbo Liangbc
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a Department of Urology, Peking University First Hospital, Beijing, China b Institute of Urology, Peking University, Beijing, China c National Urological Cancer Center, Beijing, China d Air Force General Hospital, PLA, Beijing, China e Department of Urology, Peking Union Medical College Hospital, Beijing, China f Department of Urology, Beijing Chao-Yang Hospital, Beijing, China g Department of Urology, Armed-Police General Hospital, Beijing, China h Department of Urology, Shanxi Medical University First Hospital, Taiyuan, China i Department of Urology, Hebei Medical University Second Hospital, Shijiazhuang, China j Department of Urology, The General Hospital of the People’s Liberation Army, Beijing, China k Department of Urology, First Affiliated Hospital of Jilin University, Changchun, China l Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China m Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China n Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China o Department of Urology, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China p Department of Urology, West China School of Medicine, Chengdu, China q Department of Urology, Shangdong Province-owned Hospital, Jinan, China r Department of Urology, Peking University Shenzhen Hospital, Shenzhen, China s Department of Urology, The Central Hospital of Jinan City, Jinan, China t Department of Urology, Shanghai Changzheng Hospital, Shanghai, China u Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China v Department of Urology, Beijing Anzhen Hospital of Capital Medical University, Beijing, China w Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China x Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China y Department of Urology, People’s Hospital of Xinjiang Uygur Autonomous Region, Wulumuqi, China z Department of Urology, Guangdong General Hospital, Guangzhou, China aa Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China ab Department of Urology, The First Hospital of Zhejiang Province, Hangzhou, China ac Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China ad Department of Urology, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing, China ae Department of Urology, Mianyang Central Hospital, Mianyang, China af Department of Urology, General Hospital of PLA General Staff Headquarters, Beijing, China ag Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, China ah Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China ai Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China aj Department of Urology, Xiangya Hospital of Central South University, Changsha, China ak Department of Urology, Peking University Third Hospital, Beijing, China al Department of Urology, Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China am Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China an Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ao Department of Urology, Beijing Friendship Hospital of Capital Medical University, Beijing, China ap Department of Urology, Wenzhou Central Hospital, Wenzhou, China aq Department of Urology, Peking University People’s Hospital, Beijing, China ar Department of Urology, The First Hospital of China Medical University, Shenyang, China as Department of Urology, Qinghai Province People’s Hospital, Xining, China at Department of Urology, Beijing Tongren Hospital of Capital Medical University, Beijing, China au Department of Urology, Qilu Hospital of Shandong University, Jinan, China av Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China aw Department of Urology, Tianjing Medical University General Hospital, Tianjin, China ax Department of Urology, Shanghai General Hospital, Shanghai, China ay Department of Urology, Beijing Hospital, Beijing, China az Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China ba Department of Urology, Southwest Hospital, Chongqing, China bb Department of Urology, Lanzhou University Second Hospital, Lanzhou, China bc Department of Urology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China |
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Abstract Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively (p = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively (p = 0.002). Conclusion: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.
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Received: 13 March 2017
Available online: 08 June 2018
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Corresponding Authors:
Liqun Zhou
E-mail: zhoulqmail@sina.com
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TRENDMD: |
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Cite this article: |
Liqun Zhou,Kaiwei Yang,Xuesong Li, et al. Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population☆(☆ Hospitals 1 and 3w53 were all in the study group of Fluorescence in situ hybridization in prenatal genetic diseases and cancer detection in clinical research of Chinese population.)[J]. Asian Journal of Urology,
2019, 6(1): 114-121.
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URL: |
http://www.ajurology.com/EN/10.1016/j.ajur.2018.06.001 OR http://www.ajurology.com/EN/Y2019/V6/I1/114 |
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Workflow for patient FISH and cytology. FISH, fluorescence in situ hybridization.
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| Bladder cancer | Non-bladder cancer | Total | Subjects with analyzable FISH test and cytology, n (%) | 3 640 (91.9) | 319 (8.1) | 3 959 | FISH test, n (%) | Positive | 3 011 (98.2) | 54 (1.8) | 3 065 | Negative | 629 (70.4) | 265 (29.6) | 894 | Cytology n (%) | Positive | 1 217 (98.4) | 20 (1.6) | 1 237 | Negative | 2 423 (89.0) | 299 (11.0) | 2 722 | Age (year)a | 63.04 ± 13.31 | Gender (male/female) | 3 021/938 | Diagnosed by biopsy only, n | 2 856 | Diagnosed by surgery, n | 1 103 |
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Characteristics of the cohort that presented with hematuria.
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| FISH test | Cytology | p value | True positive, n | 3 011 | 1 217 | | False positive, n | 54 | 20 | | True negative, n | 265 | 299 | | False negative, n | 629 | 2423 | | Sensitivity (%) | 82.7 | 33.4 | <0.001 | Specificity (%) | 83.1 | 93.7 | <0.001 | AUC | 0.829 | 0.636 | <0.001 | Positive predictive value (%) | 98.2 | 98.4 | | Negative predictive value (%) | 29.6 | 11.0 | |
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Comparison of FISH test and cytology in the diagnosis of all bladder transitional cell cancer (n = 3 959).
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| FISH test | Cytology | Total | p-Value | Positive | Negative | p-Value | Positive | Negative | p-Value | T stage | | 0.004 | | < 0.001 | | | Tis, n | 4 | 1 | | 2 | 3 | | 5 | | Ta, n | 205 | 49 | | 51 | 203 | | 254 | | T1, n | 277 | 59 | | 83 | 253 | | 336 | | Non-muscle invasive, n (%) | 486 (81.7) | 109 (18.3) | | 136 (22.9) | 459 (77.1) | | 595 | <0.001 | T2, n | 165 | 19 | | 69 | 115 | | 184 | | T3, n | 51 | 5 | | 23 | 33 | | 56 | | T4, n | 17 | 3 | | 11 | 9 | | 20 | | Muscle invasive, n (%) | 233 (89.6) | 27 (10.4) | | 103 (39.6) | 157 (60.4) | | 260 | <0.001 | Grade | | 0.003 | | < 0.001 | | | Low grade | 439 (82.5) | 93 (17.5) | | 116 (21.8) | 416 (78.2) | | 532 | <0.001 | High grade | 291 (90.1) | 32 (9.9) | | 137 (42.4) | 186 (57.6) | | 323 | <0.001 |
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Characteristics of all patients with valid pathological diagnoses (n = 855).
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| FISH test | Cytology | p-Value | History+ | History- | History+ | History- | True positive, n | 135 | 596 | 51 | 195 | | False positive, n | 2 | 27 | 0 | 12 | | True negative, n | 2 | 93 | 4 | 108 | | False negative, n | 25 | 99 | 112 | 497 | | Sensitivity (%) | 84.38 | 85.76 | 31.29 | 28.18 | <0.001 | Specificity (%) | 50.00 | 77.50 | 100 | 90.00 | <0.001 | Positive predictive value (%) | 98.54 | 95.67 | 100 | 94.20 | | Negative predictive value (%) | 7.40 | 48.43 | 3.44 | 17.85 | |
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The sensitivity of the FISH test in patients with or without a history of transitional cell cancer (n = 979).
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