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    [Value of fluorescence in situ hybridization of urine exfoliative cells in diagnosis of urinary bladder neoplasms]. Chen Ni,Gong Jing,Zeng Hao,Wei Qiang,Zhu Yu-chun,Chen Min,Zhou Qiao Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition OBJECTIVE:To investigate the value of fluorescence in situ hybridization (FISH) examination of urine exfoliative cells in the diagnosis of urinary bladder neoplasms. METHODS:The urine samples were collected from 100 patients with suspected urinary bladder neoplasms and 20 normal control subjects. Both FISH examination and cytology study of urine exfoliative cells were conducted with each sample. The specificity and sensitivity of FISH and cytology were analyzed on the basis of bladder biopsy histology. RESULTS:The sensitivity of FISH examination of bladder malignant tumor was 93.5% (87/93), which was much higher than that of cytology (49.5%, 46/93). Biopsies confirmed 88 cases of urothelial carcinoma among the 100 suspected patients, with 46 high grade tumors and 42 low grade tumors; 30 cases of high stage (T(2-4)) and 58 cases of low stage (T(a-1)). The sensitivity of FISH examination of urothelial carcinoma was 94.3%, which was much higher than that of cytology (52.3%). FISH examination was significantly more sensitive than cytology for low grade and low stage urothelial carcinoma, as well as for rare non-urothelial malignancies (P < 0.05). The specificity of FISH and cytology of bladder malignancies was 92.6% (25/27) and 96.3% (26/27), for urothelial carcinoma was 81.3% (26/32) and 96.9% (31/32), respectively. CONCLUSION:FISH shows high sensitivity and relatively high specificity for the detection of urinary bladder neoplasms, especially for the diagnosis of low grade urothelial carcinoma and non-urothelial malignancies, which were difficult to be detected by cytology.
    Chromosomal aberrations in bladder cancer: fresh versus formalin fixed paraffin embedded tissue and targeted FISH versus wide microarray-based CGH analysis. Panzeri Elena,Conconi Donatella,Antolini Laura,Redaelli Serena,Valsecchi Maria Grazia,Bovo Giorgio,Pallotti Francesco,Viganò Paolo,Strada Guido,Dalprà Leda,Bentivegna Angela PloS one Bladder carcinogenesis is believed to follow two alternative pathways driven by the loss of chromosome 9 and the gain of chromosome 7, albeit other nonrandom copy number alterations (CNAs) were identified. However, confirmation studies are needed since many aspects of this model remain unclear and considerable heterogeneity among cases has emerged. One of the purposes of this study was to evaluate the performance of a targeted test (UroVysion assay) widely used for the detection of Transitional Cell Carcinoma (TCC) of the bladder, in two different types of material derived from the same tumor. We compared the results of UroVysion test performed on Freshly Isolated interphasic Nuclei (FIN) and on Formalin Fixed Paraffin Embedded (FFPE) tissues from 22 TCCs and we didn't find substantial differences. A second goal was to assess the concordance between array-CGH profiles and the targeted chromosomal profiles of UroVysion assay on an additional set of 10 TCCs, in order to evaluate whether UroVysion is an adequately sensitive method for the identification of selected aneuploidies and nonrandom CNAs in TCCs. Our results confirmed the importance of global genomic screening methods, that is array based CGH, to comprehensively determine the genomic profiles of large series of TCCs tumors. However, this technique has yet some limitations, such as not being able to detect low level mosaicism, or not detecting any change in the number of copies for a kind of compensatory effect due to the presence of high cellular heterogeneity. Thus, it is still advisable to use complementary techniques such as array-CGH and FISH, as the former is able to detect alterations at the genome level not excluding any chromosome, but the latter is able to maintain the individual data at the level of single cells, even if it focuses on few genomic regions. 10.1371/journal.pone.0024237
    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. Daniely Michal,Rona Roni,Kaplan Tal,Olsfanger Shirley,Elboim Lea,Freiberger Avner,Lew Sylvia,Leibovitch Ilan Cancer 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. 10.1002/cncr.23119
    [Predictive value of fluorescence in situ hybridization in patients with bladder cancer]. Shan Zheng-fei,Zheng Shao-bin,Wu Peng,Tan Wan-long,Zuo Yi,Zhou Hai-kuan,Qi Huan,Zhang Peng,Peng Hong-mei Nan fang yi ke da xue xue bao = Journal of Southern Medical University OBJECTIVE:To assess the value of fluorescence in situ hybridization (FISH) in the diagnosis of bladder cancer. METHODS:Urine samples from 100 patients suspected of having bladder cancer were collected before cystoscopy for immediate urine cytology and FISH analysis. The criteria for FISH abnormality were determined by evaluating the urine specimens from 20 subjects without urogenital neoplasm. RESULTS:The overall sensitivity of cytology and FISH was 43.2% and 82.4%, and their specificity was 92.3% and 88.5%, with diagnostic concordance rate of 56.0% and 84.0%, respectively. The differences between FISH and cytology showed statistical significance in the sensitivity, diagnostic concordance rate, non-muscle-invasive cancer and primary cancer. CONCLUSION:The sensitivity and efficiency of FISH in the detection of bladder cancer are superior to those of cytology, especially for prophase cancer.
    The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus Calmette-Guérin therapy. Savic Spasenija,Zlobec Inti,Thalmann George N,Engeler Daniel,Schmauss Martina,Lehmann Kurt,Mattarelli Gianfranco,Eichenberger Tobias,Dalquen Peter,Spieler Peter,Schoenegg René,Gasser Thomas C,Sulser Tullio,Forster Thomas,Zellweger Tobias,Casella Roberto,Bubendorf Lukas International journal of cancer Molecular markers reliably predicting failure or success of Bacillus Calmette-Guérin (BCG) in the treatment of nonmuscle-invasive urothelial bladder cancer (NMIBC) are lacking. The aim of our study was to evaluate the value of cytology and chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in predicting failure to BCG therapy. Sixty-eight patients with NMIBC were prospectively recruited. Bladder washings collected before and after BCG instillation were analyzed by conventional cytology and by multitarget FISH assay (UroVysion, Abbott/Vysis, Des Plaines, IL) for aberrations of chromosomes 3, 7, 17 and 9p21. Persistent and recurrent bladder cancers were defined as positive events during follow-up. Twenty-six of 68 (38%) NMIBC failed to BCG. Both positive post-BCG cytology and positive post-BCG FISH were significantly associated with failure of BCG (hazard ratio (HR)= 5.1 and HR= 5.6, respectively; p < 0.001 each) when compared to those with negative results. In the subgroup of nondefinitive cytology (all except those with unequivocally positive cytology), FISH was superior to cytology as a marker of relapse (HR= 6.2 and 1.4, respectively). Cytology and FISH in post-BCG bladder washings are highly interrelated and a positive result predicts failure to BCG therapy in patients with NMIBC equally well. FISH is most useful in the diagnostically less certain cytology categories but does not provide additional information in clearly malignant cytology. 10.1002/ijc.24258
    Role of fluorescence in situ hybridization in bladder cancer surveillance of patients with negative cytology. Youssef Ramy F,Schlomer Bruce J,Ho Richard,Sagalowsky Arthur I,Ashfaq Raheela,Lotan Yair Urologic oncology OBJECTIVES:The clinical utility of urine markers in urothelial cancer (UC) surveillance is not established. We previously evaluated the use of fluorescence in situ hybridization (FISH) in managing patients with atypical cytology at risk for UC. This study evaluates its role in patients with negative cytology with a history of UC. MATERIALS AND METHODS:Between June 2007 and January 2009, every patient with a history of UC who underwent cystoscopy and cytology with UroVysion test were identified. A comprehensive chart review was performed on each patient with negative cytology. RESULTS:The population comprised 142 patients undergoing cancer surveillance; 111 patients with negative cystoscopy, 19 with equivocal cystoscopy, and 12 with positive cystoscopy. In patients with negative cystoscopy, there was cancer in only 1 of 111 patients. UroVysion could detect the only patient with UC with sensitivity of 100% and had a negative predictive value (NPV) of 100%. In patients with equivocal cystoscopy, it detected 2 tumors that would be missed by cytology. There were 4 false negative results (sensitivity 33.3% and NPV 66.7%). In patients with obvious lesion on cystoscopy, there were 9 false negative results (sensitivity 10% and NPV 18.2%). CONCLUSIONS:Few patients with negative cystoscopy and negative cytology have cancer. Patients with equivocal and positive cystoscopy and negative cytology frequently have cancer and the UroVysion FISH assay was not helpful in these cases. The cost-effectiveness of the FISH assay needs to be assessed prior to widespread use in patients with negative cytology. 10.1016/j.urolonc.2010.02.012
    Quantitative fluorescence in situ hybridization and its ability to predict bladder cancer recurrence and progression to muscle-invasive bladder cancer. Kipp Benjamin R,Tanasescu Mihaela,Else Terry A,Bryant Sandra C,Karnes R Jeffrey,Sebo Thomas J,Halling Kevin C The Journal of molecular diagnostics : JMD Fluorescence in situ hybridization (FISH) testing is used to detect bladder cancer in urine specimens. The purpose of this study was to determine whether there are associations between the percentage of chromosomally abnormal cells by FISH and time to bladder cancer recurrence and progression to metastasis. Clinical records were searched to identify patients with urine FISH results, history of non-invasive bladder cancer, and at least one follow-up pathological diagnosis. Covariates analyzed included age, gender, smoking status, treatment after FISH, cystoscopy result, and prior stage of bladder cancer. The percentage of abnormal cells (hazard ratio [HR] 1.03, 95% CI 1.02-1.03; P < 0.001), age (HR 1.02, 95% CI 1.00-1.03; P = 0.033), male gender (HR 0.60, 95% CI 0.41-0.87; P < 0.001), treatment (HR 0.37, 95% CI 0.25-0.55; P < 0.001), and history of TIS/T1-stage tumors (HR 1.66, 95% CI 1.23-2.24; P = 0.001) were significantly associated with time to cancer recurrence. Time to invasive cancer was significantly associated with the percentage of abnormal cells (HR 1.02, 95% CI 1.01, 1.03; P < 0.001), history of TIS/T1 tumor (HR 3.73, 95% CI 1.88, 7.38; P = 0.001), and treatment (HR 0.33, 95% CI 0.13, 0.83; P = 0.019), suggesting that the percentage of abnormal cells independently predicts cancer recurrence and progression to invasive disease in patients with a history of non-invasive bladder cancer. 10.2353/jmoldx.2009.080096
    Analysis of fluorescence in situ hybridization, mtDNA quantification, and mtDNA sequence for the detection of early bladder cancer. Yoo Jong-Ha,Suh Borum,Park Tae Sung,Shin Myung-Geun,Choi Yeung Deuk,Lee Chang Hoon,Choi Jong Rak Cancer genetics and cytogenetics We designed this study to test the sensitivities of cytology, the nuclear matrix protein 22 (NMP22) assay, and fluorescence in situ hybridization (FISH) in the early detection of urothelial carcinoma, and to identify mtDNA alterations in urinary epithelial cells. We collected 41 urine samples and 26 corresponding peripheral blood samples from patients with clinically suspected urothelial carcinoma. The FISH and NMP22 assays detected 92.1% of the cancers, and cytology detected 60.5%. In the low-grade group, NMP22 and FISH analyses were more sensitive than cytology, but in the high-grade group, all three methods showed approximately 90% sensitivity. Overall, the FISH and NMP22, or FISH and cytology assays combined detected 97.4% of cancers, while cytology with NMP22 detected 92.1%. In the low-grade group, the sensitivity of the three methods combined was above 80%, but in high-grade group, the combined sensitivity was approximately 100%. In the mtDNA control region, we detected characteristic heteroplasmic mtDNA substitution mutations in 1 patient and a mtDNA length heteroplasmic mutation in 303 polyC or 16184 poly C in 20 patients. Overall, urothelial carcinoma-specific mtDNA mutations were observed in 20 of the 26 patients (76.9%). The average mtDNA copy numbers in urine samples and corresponding peripheral blood samples (83.45 +/- 60.36 and 39.0 +/- 24.38, respectively) (mean +/- standard deviation [SD]) differed significantly (P < 0.001). The mtDNA copy numbers in the urine samples from patients with high-grade and low-grade tumors (81.83 +/- 67.78 and 86.49 +/- 46.69, respectively) did not differ significantly (P = 0.589). In conclusion, the FISH assay showed the highest sensitivity for detecting low-grade urothelial carcinoma, and mtDNA copy numbers in urine samples were higher than those in the corresponding peripheral blood samples. The frequency of mtDNA mutations in the D-loop region in patients with cancer was approximately 80% in our study. This report further supports the significance of genetic alteration in urothelial carcinoma and the clinical utility of the FISH, mtDNA quantitation polymerase chain reaction, mtDNA sequencing, and capillary electrophoresis for this purpose. 10.1016/j.cancergencyto.2009.12.017
    [Early diagnostics of bladder cancer recurrence with fluorescence in situ hybridization method in the first 24 months after a transurethral resection of a bladder in old and elderly persons]. Pushkin A S,Ryzhak G A Advances in gerontology = Uspekhi gerontologii This article presents the results of experience of application of a technique fluorescent in situ hybridization (FISH) in early diagnostics of relapses of a superficial bladder cancer in 103 middle-aged, old and senile persons who had transurethral resection of the bladder.
    Applicability of the FISH test for bladder cancer. Ward-Smith Peggy,Miller Brenda,Caughron Michael Urologic nursing Fluorescence in situ hybridization (FISH) analysis is an FDA-approved, urine-based marker that assists in diagnosis and surveillance of invasive urothelial cancer. This article provides an overview and case study demonstrating the clinical use of this analysis. As a systematic review of non-randomized and randomized clinical trials, this article provides Level I evidence.
    Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer. Maffezzini Massimo,Campodonico Fabio,Capponi Giacomo,Canepa Giorgio,Casazza Stefania,Bandelloni Roberto,Tamagno Stefania,Puntoni Matteo Anticancer research AIM:To evaluate the potential contribution of a fluorescent in situ hybridization (FISH) as prognostic indicator of the risk of recurrence or progression in patients undergoing follow-up for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS:A total of 126 consecutive patients with a history of NMIBC being followed-up with urinary cytology and cystoscopy at a referral centre were studied. Patients with carcinoma in situ, or tumour stage higher than pT1 were excluded. A UroVysion FISH kit was used to detect four chromosomal abnormalities, specifically, locus 9p21, Ch 3, 7, and 17. Three FISH patterns were defined: negative; low-risk positive, i.e. positive staining for 9p21 and/or Ch3 abnormalities; and high-risk positive, i.e. positive staining for Ch7 and/or 17. RESULTS:Overall 73 out of 126 patients (57.9%) had a positive urinary FISH test. After a median time of 14 months, 46 FISH-positive patients underwent recurrence (36.5%) and in 15 patients there was progression of disease (11.9%). Among positive patients, the low-risk category was found in 34, and the high-risk in 39. Low-risk FISH-positive patients had a higher rate of recurrence as compared to FISH-negative patients, with a hazard ratio (HR) of 1.6. The recurrence rate was even greater in patients with a high-risk positive test, with an HR of 1.9. The limitation of the study was that the impact of intravesical treatment was not assessed. CONCLUSION:The urinary FISH test can be used as an aid in predicting the risk of recurrence during follow-up of patients with history of NMIBC.
    [Detection of bladder cancer by FISH test: a meta-analysis]. Zeng Zheng,Zhou Xiao-jun Zhonghua bing li xue za zhi = Chinese journal of pathology OBJECTIVE:To compare the diagnostic value of fluorescence in-situ hybridization (FISH) and traditional cytology in detection of bladder cancer, and to evaluate if FISH test is superior to cytologic examination in this respect. METHODS:The electronic database of PubMed was searched. Criteria for inclusion and exclusion into the meta-analysis were established. The studies fulfilling the inclusion criteria were selected. Data of these studies were extracted for calculation of pooled odds ratio, likelihood ratio, sensitivity and specificity. Summary receiver operating curve and area under curve (AUC) were produced with Meta-DiSc software. RESULTS:Fourteen studies were included, and data related to cytologic examination were available in nine of them. The pooled sensitivity and specificity of FISH test were 0.69 (95%CI 0.66 to 0.73) and 0.84 (95%CI 0.81 to 0.86), respectively. The pooled sensitivity and specificity of cytology were 0.46 (95%CI 0.42 to 0.51) and 0.88 (95%CI 0.84 to 0.90), respectively. The AUC for FISH and cytology were 0.87 and 0.81, respectively. The difference in AUC between the two tests was not statistically significant (P > 0.05). CONCLUSIONS:Comparing with traditional cytological examination, FISH test is more sensitive. However, FISH test is still not proven to have better diagnostic value in detection of bladder cancer in both new and follow-up cases. More studies in this area are required for further evaluation.
    Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for the detection of bladder cancer. Junker K,Fritsch T,Hartmann A,Schulze W,Schubert J Cytogenetic and genome research Bladder cancer is the fifth most common cancer in adults. Because of the high recurrence rate (up to 70%) new tumor markers for urine are necessary for monitoring patients. In this study, we investigated the value of M-FISH on cells from urine for the detection of bladder cancer. Urine samples from 141 patients suspicious of bladder cancer were analyzed in this study. Cells were isolated from urine before surgical therapy. For FISH analysis, a commercial kit (UroVysion) containing hybridization probes for chromosomes 3, 7, 9p21 and 17, was used. Twenty-five cells were analyzed in each case by two observers. A FISH result was obtained in 121 cases. Overall, sensitivity was 60% and specificity reached 82.6%. Sensitivity and specificity by cytology were 24.1% and 90.5%, respectively. Analyzing results concerning T-category, sensitivity of FISH and cytology was 36.1% and 15% in pTa, 65.2 and 25.7% in pT1, 100% and 66.7% in pT2-3 tumors, respectively. Concerning tumor grade, similar results were obtained: sensitivity was 37% and 14% in G1, 65.4% and 40% in G2, 91.7% and 50% in G3 tumors, for FISH and cytology, respectively. In conclusion, FISH on cells from urine has been shown in all studies to be highly sensitive and specific for detection of bladder cancer. Sensitivity of FISH is higher than conventional cytology and can be used in routine diagnosis additionally to conventional cytology especially in doubtful or negative cases. FISH can detect recurrence earlier than other methods like cytology, cystoscopy or biopsy histological examination. 10.1159/000094214
    [Meta-analysis of fluorescence in situ hybridization and cytology for diagnosis of bladder cancer]. Yang Ming-Gen,Zhao Xiao-Kun,Hou Yi,Xiao Ning Ai zheng = Aizheng = Chinese journal of cancer BACKGROUND AND OBJECTIVE:Currently, cystoscopy and urine cytology are standard modalities in therapy monitoring and follow-up of bladder cancer. Cystoscopy is an invasive and uncomfortable procedure while cytology has a limited value because it is operator-dependent and has a low sensitivity. This study was to assess the accuracy of fluorescence in situ hybridization(FISH) in detecting bladder cancer by comparing it with cytology using systemic analyses of studies published in both English and Chinese. METHODS:Cochrane systematic evaluation was used to search through MEDLINE, EMBASE, Cochrane Library, CMCC and CNKI for studies regarding FISH and cytology in the detection of bladder cancer. Data were extracted and analyzed using software MetaDiSc1.4. RESULTS:In total 242 relevant studies were searched, of which 12 studies were enrolled and 3430 patients were included. Heterogeneity, except for threshold effects, was found within these studies. A meta-analysis was performed using the random effect model. Pooled accuracy indicators like sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio of FISH and cytology were 74% (71%-77%) vs. 57% (54%-61%), 88 % (86%-90%) vs. 85 % (83%-87%), 6.18 (3.56-10.73) vs. 4.15 (2.78-6.20), 0.29 (0.19-0.45) vs. 0.51(0.41-0.63) and 24.17 (9.33-62.64) vs. 9.59 (5.91-15.57), respectively. The sensitivity of both FISH and cytology were increased with the increase of tumor grade and stage. The areas under summary receiver operating characteristics (SROC) curve were 0.8938 and 0.7847, and the Q indices were 0.8247 and 0.7226 for FISH and cytology, respectively. CONCLUSIONS:FISH has a high accuracy in detecting bladder cancer. But its sensitivity in detecting high-stage bladder cancer is lower than that of cytology. Although FISH can not replace traditional urine cytology, it can be used as an important adjunct in the preoperative detection and postoperative monitoring of bladder cancer.
    Does polyomavirus infection interfere with bladder cancer fluorescence in situ hybridization? Hossain Deloar,Hull David,Kalantarpour Fatemeh,Maitlen Rebecca,Qian Junqi,Bostwick David G Diagnostic cytopathology Urine cytology is a proven and widely used screening tool for the detection of urothelial carcinoma. However, morphologic features of polyomavirus infected cells, characterized by nuclear inclusions (decoy cells) are a known source of diagnostic confusion with malignancy. Fluorescence in situ hybridization (FISH) is now routinely used to support the cytological diagnosis of urothelial carcinoma and monitor for recurrence. We sought to determine whether polyomavirus infection could result in positive FISH results (aneuploidy). This study deals with retrospective study of 100 polyomavirus-infected urine samples from patients with no history of urothelial carcinoma or organ transplantation. All cases were stained with Papanicolaou and acid hematoxylin stain. One slide from each sample was de-stained and FISH was performed using chromosome enumeration probes 3, 7, 17, and locus-specific probe 9p21. Adequate cells for FISH analysis (25 cells) were present in 81 cases; 19 cases were insufficient due to loss of cells during de-staining and FISH preparation process. All polyomavirus-infected cells (decoy cells) exhibited a normal chromosome pattern. Four cases were FISH positive, but there were no positive decoy cells. Decoy cells did not exhibit aneuploidy by FISH. The presence of decoy cells does not exclude the possibility of concurrent urothelial carcinoma. Acid hematoxylin stain appeared to supplement the Papanicolou stain in identifying and confirming the presence of polyomavirus infection. 10.1002/dc.23027
    Clinical usefulness of fluorescence in situ hybridization for diagnosis and surveillance of bladder cancer. Song Min-Jung,Lee Hyun-Moo,Kim Sun-Hee Cancer genetics and cytogenetics We evaluated the performance of the fluorescence in situ hybridization (FISH) assay in comparison with that of urinary cytology for the detection of bladder urothelial carcinoma in routine clinical practice. Voided urine samples from 602 patients with hematuria were analyzed. The bladder cancer group consisted of 95 patients who had biopsy-proven bladder cancer, and the control group consisted of 507 patients without bladder cancer. We found a significant difference between the overall sensitivities of FISH and cytology (60% vs. 28.4%, respectively; P < 0.0001). The overall specificity was 99% with cytology and 94.9% with FISH, although this difference was not statistically significant. The mean values for all four probes in the true-positive group were higher than those in the false-positive group. The difference in the mean values between the two groups was significant only for the CEP3 and CEP17 probes. Furthermore, the severity of the genetic alterations detected by FISH showed a positive correlation with both tumor invasiveness (stage Ta --> T1, T2) and histological grade (G1, G2 --> G3). Together, these findings suggest that FISH can be a useful diagnostic and surveillance tool for patients who are suspected of having new or recurrent bladder cancer. 10.1016/j.cancergencyto.2010.01.007
    Fluorescence in situ hybridization (FISH) in the diagnosis of bladder and upper tract urothelial carcinoma: the largest single-institution experience to date. Gomella Leonard G,Mann Mark J,Cleary Ryan C,Hubosky Scott G,Bagley Demetrius H,Thumar Adeep B,McCue Peter A,Lallas Costas D,Trabulsi Edouard J The Canadian journal of urology INTRODUCTION:We evaluated the UroVysion (Abbott Molecular, IL, USA) fluorescence in situ hybridization (FISH) assay for the diagnosis of urothelial cancer in patients diagnosed with or suspected to have bladder, upper tract urothelial carcinoma (UTUC), and combined upper and lower tract urothelial carcinoma (BC). MATERIALS AND METHODS:A single institution retrospective analysis comparing sensitivity, specificity, positive predictive value, and negative predictive values for FISH and urinary cytology. FISH within 6 months of endoscopic evaluation were obtained from outpatient voided urine samples. Our institutional pathology department confirmed pathologic disease from specimens obtained during endoscopic evaluations for lower tract disease. For upper tract disease, disease was confirmed by retrograde ureteroscopy, biopsies of visual lesions, and site-specific upper tract cytology. RESULTS:A total of 415 patients submitted FISH specimens. Overall, FISH was more sensitive than cytology 54.9% in comparison with cytology 42.2% (p = 0.01), specificity favored cytology 92.9% compared to 73.5% with FISH (p < 0.01). For BC only patients, the same significant finding of increased sensitivity and decreased specificity was identified, but for UTUC alone and combined UTUC and BC, there was no significant difference. Cytology had improved positive predictive value (PPV) over FISH, 76.9% in comparison to 64.6% (p = 0.02). Negative predictive value (NPV) also favored cytology 74.2% versus 64.9% (p = 0.02). When analyzing individual cohorts, cytology had improved PPV for BC alone patients. UTUC showed no difference for PPV and NPV. For both UTUC and BC, NPV was slightly favored for FISH over cytology 93.2% versus 91.2% (p = 0.03). CONCLUSIONS:Voided urine FISH testing does offer a higher detection of urothelial carcinoma for BC compared to voided cytology; however, specificity was worse. FISH does not appear to improve detection of urothelial carcinoma in patients with either UTUC only or both BC and UTUC.
    Urovysion FISH Could Be Effective and Useful Method to Confirm the Identity of Cultured Circulating Tumor Cells from Bladder Cancer Patients. Kim Tae-Jung,Moon Hyong Woo,Kang Sungmin,Yang Jonghyup,Hong Sung-Hoo,Lee Ji Youl,Ha U-Syn Journal of Cancer : To explore whether cultured CTC from bladder-cancer patients originate from bladder cancer and share chromosomal abnormalities, by means of a fluorescence hybridization (FISH) test. : A total of 15 ml of blood was collected from the patients with bladder cancer before treatment began. Isolated CTCs were divided into 5 ml for CTC enumeration and 10 ml for CTC culture. CTCs were counted by immunofluorescent staining with vimentin, cytokeratin, CD45, and DAPI antibody. CTCs were cultured using isolated CTCs in 96-well plates of Mesenchymal Stem Cell Growth Medium for 16~18 days. The resulting cultured CTCs from 20 men with bladder cancer were analyzed by Urovysion FISH. : Common gains were on chromosome 3, 7, and 17 in 20 (74.1%), 14 (51.9%), and 20 (74.1%) of 27 patients, respectively. Polysomy was detected on chromosomes 3 and 7 in 9 patients (33.3%). Polysomy involving two chromosomes was observed in 16 (59.3%, chromosome 3 and 17) and 9 patients (33.3%, chromosome 7 and 17) in the same cell. Among the patients with isolated gain, 17 (63.0%) met the positive criteria for Urovysion FISH. Homozygous deletion of 9p21, 5 (18.5%) involved more than 12 cells. Among the different patient cohorts, positive results based on the Urovysion criteria were obtained in cultured CTCs derived from 19 (70.4%) patients. : Application of FISH Urovysion to cultured CTCs from bladder cancer could be an effective first step to confirm their origin and sharing of chromosomal abnormalities. 10.7150/jca.30079
    Bladder cancer detection using FISH (UroVysion assay). Halling Kevin C,Kipp Benjamin R Advances in anatomic pathology UroVysion is a fluorescence in situ hybridization assay that was developed for the detection of bladder cancer in urine specimens. It consists of fluorescently labeled DNA probes to the pericentromeric regions of chromosomes 3 (red), 7 (green), and 17 (aqua) and to the 9p21 band (gold) location of the P16 tumor suppressor gene. The UroVysion assay works by detecting urinary cells that have chromosomal abnormalities consistent with a diagnosis of bladder cancer. Studies have shown that UroVysion is more sensitive than urine cytology for the detection of all stages and grades of bladder cancer. UroVysion is Food and Drug Administration-approved for the detection of recurrent bladder cancer in voided urine specimens from patients with a history of bladder cancer and for the detection of bladder cancer in voided urine specimens from patients with gross or microscopic hematuria, but no previous history of bladder cancer. Recent studies also suggest that UroVysion may be useful for assessing superficial bladder cancer patients' response to bacillus Calmette-Guerin therapy and in detecting upper tract urothelial carcinoma. 10.1097/PAP.0b013e3181832320
    [Comparative evaluation of the predictive value of UroVysion and AURKA FISH tests of urine sediment cells for the diagnosis of bladder cancer]. Vorobtsova I E,Kouzova E D,Kolesnikova I S Voprosy onkologii Informative value of two tests based on FISH of exfoliated urothelial cells in urine sediment (AURKA and UroVysion) was compared in the group of patients (31 persons) with the history of bladder cancer. Coincidence in results of both FISH assays was found in 93.5%. These preliminary data offer the possibility of replacing the expensive UroVysion kit by the less expensive AURKA FISH probe and it could be used for monitoring of recurrence in bladder cancer patients.
    The value of the preoperative FISH test in unscreened bladder cancer patients with TUR indications. Petrov S V,Malkhasyan K A,Ulyanin M Yu,Abdrakhmanov E F,Khasanov R Sh Pathology oncology research : POR Patients with bladder cancer are still requiring close follow up with frequent cystoscopies. This study aims to assess the FISH analysis, as a procedure capable of highlighting the hidden features of a tumor and helping to individualize treatment tactics. The bladder washings of 50 primary bladder cancer patients were taken prior to TURB and analyzed with the commercial FISH assay UroVysion®. All patients were divided into groups according to the maximum stage and grade of the tumor. The sensitivity of the method was 81.5 %, 91.7 % and 100 % for the Ta, T1 and T2 stage groups, respectively. For the G1, G2 and G3 groups the sensitivity was 70 %, 100 % and 100 %, respectively. In addition, the rate of detecting genetically abnormal cells was significantly higher in the T2 stage compared to the Ta and combined Ta+T1 groups, as well as in the G3 group compared to the G1 and G2 groups. The mean signal number from each chromosome insignificantly increased with the stage and grade of the tumor. The detection of <40 % genetically abnormal cells predicted the absence of muscle invasion and a G3 tumor with more then 90 % reliability. The FISH method is highly sensitive in early bladder cancer detection and is able to predict the morphological character of a tumor even before surgery. 10.1007/s12253-012-9544-6
    Long-term follow-up of intermediate-risk non-muscle invasive bladder cancer sub-classified by multi-coloured FISH. Mian Christine,Comploj Evi,Resnyak Elisabeth,Trenti Emanuela,Palermo Salvatore,Lodde Michele,Pycha Alexander,Ambrosini-Spaltro Andrea,Dechet Christopher B,Pycha Armin Anticancer research AIM:To examine the long-term follow-up of patients with that previously underwent risk stratification based on multicolour FISH testing. PATIENTS AND METHODS:On 81 patients with intermediate-risk urothelial carcinoma, a multicolour-FISH was performed. Patients were sub-divided into low- and high-risk groups based on chromosomal patterns. Univariate analysis, using Mantel-Cox log-rank test for disease-free, progression-free survival and overall survival, was employed to determine the prognostic significance of FISH analysis. Survival times were calculated according to the Kaplan-Meier product-limit method and multivariate analysis using Cox proportional hazards regression model. RESULTS:The univariate Mantel-Cox log-rank test showed significant differences between the low-risk and the high-risk group for disease-free survival (p=0.005) and overall survival (p=0.038), but not for progression-free survival (p=0.129). CONCLUSION:Our long-term follow-up data appear to be able to divide tumors into low and high risk groups for recurrence based on molecular/genetic changes observed with FISH.
    Anticipatory Positive Urine Tests for Bladder Cancer. Gopalakrishna Ajay,Fantony Joseph J,Longo Thomas A,Owusu Richmond,Foo Wen-Chi,Dash Rajesh,Denton Brian T,Inman Brant A Annals of surgical oncology PURPOSE:The aim of this study was to establish the criteria defining an anticipatory positive test for bladder cancer. METHODS:We reviewed all patients at our institution who underwent urine cytology or UroVysion fluorescence in situ hybridization (FISH) and cystoscopy from 2003 to 2012. Test performance and cancer anticipation was assessed using generalized linear mixed models, mixed-effects proportional hazards models, and cumulative incidence curves using tests performed within 30 days of each other as well as within a lag time of 1 year. RESULTS:Overall, 6729 urine tests (4729 cytology and 2040 UroVysion FISH) were paired with gold-standard cystoscopies. Sensitivity and specificity were 63 and 41% for cytology, and 37 and 84% for UroVysion FISH, respectively. A 1-year lag time allowed for cancer anticipation and neither test improved. Among patients with positive cytology and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.83; 76% of these patients developed a tumor within 1 year. Similarly, among patients with a positive FISH and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.56; 40% of these patients developed a tumor within 1 year. CONCLUSIONS:Urine-based tests for bladder cancer are frequently falsely positive. With further follow-up time, some of these false positive tests are vindicated as true (anticipatory) positive tests, although many will remain false positives. We developed statistical criteria to determine if a test anticipates future cancers or not. 10.1245/s10434-016-5763-5
    Copy number aberrations using multicolour fluorescence in situ hybridization (FISH) for prognostication in non-muscle-invasive bladder cancer (NIMBC). Matsuyama Hideyasu,Ikemoto Kenzo,Eguchi Satoshi,Oga Atsunori,Kawauchi Shigeto,Yamamoto Yoshiaki,Kawai Yoshihisa,Matsumoto Hiroaki,Hara Takahiko,Nagao Kazuhiro,Sakano Shigeru,Sasaki Kohsuke BJU international OBJECTIVE:To investigate if detection of copy number aberrations of chromosomes 3, 7, 9p21, and 17 using multicolour fluorescence in situ hybridization (FISH) predicts patient outcome in non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS:In all, 118 bladder wash samples were prospectively collected from patients who underwent transurethral resection of bladder tumour (median age 50.5 years, male/female: 91/27, tumour grade 1/2/3: 18/52/42, stage pTis/Ta/T1: 8/62/42) from 2007 to 2010. The 118 samples were analysed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 9p21, and 17. The variant fraction (VF; the sum of the non-modal copy number fraction of each chromosome) was defined as abnormal when the percentage was ≥16%. The percentage deletion of 9p21 (fraction of null or one copy number of the 9p21 locus) was defined as abnormal when the percentage was ≥12%. Maffezzini risk criteria were also analysed in our cohorts. RESULTS:There was recurrence in 57 (48.3%) patients and disease progression in 12 (10.1%), with a median follow-up of 35.7 months. Multivariate analysis showed that the percentage 9p21 loss (>12%) was an independent prognostic factor for recurrence (P < 0.001, odds ratio [OR] 3.24, 95% confidence interval [CI] 1.85-5.62). For disease progression, tumour grade, positive urine cytology, concurrent carcinoma in situ, and a mean VF of >16% were significant prognostic factors in univariate analysis. In multivariate analysis, a mean VF of >16% was a prognostic factor for disease progression (P = 0.048, OR 6.07, 95% CI 1.02-57.45). CONCLUSIONS:Multicolour-FISH analysis using a commercially available kit could be a powerful tool not only for diagnosis, but also for prognostication in patients with NMIBC. 10.1111/bju.12232
    Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer. Kehinde Elijah O,Al-Mulla Fahd,Kapila Kusum,Anim Jehoram T Scandinavian journal of urology and nephrology OBJECTIVE:This study aimed to compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of urine cytology, BladderChek® nuclear matrix protein-22 (NMP22) and UroVysion™ fluorescence in situ hybridization (FISH) tests in patients with newly diagnosed bladder cancer, those with recurrent bladder cancer, and those with bladder cancer but in remission during surveillance. MATERIAL AND METHODS:Voided urine samples obtained from 178 patients with suspected or known bladder cancer about to undergo diagnostic or surveillance cystoscopy and 25 control subjects without the disease were divided into four and used for urine culture and cytology, NMP22 BladderChek and UroVysion FISH tests. The sensitivity, specificity, PPV and NPV for each test were calculated. Comparison was made between the ability of each test to detect bladder cancer in the three category of patients listed. RESULTS:Of the 178 patients with bladder cancer, 43 were newly diagnosed, 58 had recurrent disease and 77 were in remission. The sensitivity of each test in newly diagnosed patients was: urine cytology 28%, NMP22 88% and FISH 80%; and in patients with recurrent disease: urine cytology 33%, NMP22 57% and FISH 85%. The mean specificity for urine cytology, NMP22 and FISH was 95%, 67% and 48%, respectively. CONCLUSION:Of the tests used in the study for detection of bladder cancer, NMP22 appeared to be most cost-effective and rapid, with relatively high sensitivity and specificity in all categories of patients. The NMP22 test may be considered a new gold standard for the assessment of patients with known or suspected bladder cancer. 10.3109/00365599.2010.533694
    The role of fluorescence in situ hybridization to predict patient response to intravesical Bacillus Calmette-Guérin therapy for bladder cancer: A diagnostic meta-analysis and systematic review. Bao Yige,Tu Xiang,Chang Tiancong,Qiu Shi,Yang Lu,Geng Jiwen,Quan Liuliu,Wei Qiang Medicine BACKGROUND:The aim of the study was to systematically review the relevant studies to assess the role of fluorescence in situ hybridization (FISH) test for predicting patient response to Bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT). METHODS:We searched PubMed, Embase, and the Cochrane Library from inception to July 5, 2018, and used Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We pooled sensitivity, specificity, and area under curve (AUC) of baseline and post-BCG FISH test for predicting tumor recurrence. Hazard ratio (HR) with 95% confidence intervals (95% CIs) and a Fagan nomogram were applied to assess predictive accuracy of post-BCG FISH test. RESULTS:A total of 6 studies with 442 participants for post-BCG test and 404 participants for baseline BCG test were included. The pooled analysis for post-BCG FISH test revealed the sensitivity of 0.54 (95% CI 0.38-0.69), specificity of 0.84 (95% CI: 0.72-0.91), and area under the curve (AUC) of 0.78 (95% CI: 0.74-0.81) for predicting tumor recurrence. Patients with positive post-BCG FISH test were more likely to recur during follow-up (HR 3.95, 95% CI 2.72-5.72). The Fagan nomogram revealed the "post-test" probability of tumor recurrence increased by 29% for patients with positive post-BCG FISH test. The baseline FISH test had a pooled sensitivity of 0.70 (95% CI 0.55-0.81), specificity of 0.41 (95% CI: 0.26-0.58), and AUC of 0.60 (95% CI: 0.56-0.64) for predicting recurrence. CONCLUSION:The post-BCG FISH test can predict BCG failure with high specificity and patients with positive post-BCG FISH test were more likely to recur. However, the relatively low sensitivity of post-BCG FISH test and unsatisfactory performance of baseline FISH test may limit their mono-use. 10.1097/MD.0000000000012227
    No influence of smoking status on the performance of urine markers for the detection of bladder cancer. Deininger Susanne,Hennenlotter J,Rausch S,Docktor K,Neumann E,da Costa I A,Bedke J,Stenzl A,Todenhöfer T Journal of cancer research and clinical oncology PURPOSE:The performance of urinary markers for detecting bladder cancer (BC) is influenced by various factors. The aim of the present study was to evaluate the influence of smoking habits on the performance of four commonly used urine markers. METHODS:Urine samples of 723 patients with suspected BC were analysed using urine cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+ test), and quantitative nuclear matrix protein 22 (NMP22) immunoassay. The smoking habits of all patients were recorded and a cystoscopy performed within 2 weeks after urinary marker testing. Rates of false negative and false positive results were compared between non-smokers, former smokers, and current smokers by contingency analyses. RESULTS:We included 723 patients in this study, 431 (59.6%) of which were non-smokers, 215 former smokers (29.7%), and 77 (10.7%) current smokers. 148 patients (20.5%) had a tumour at the time of urinary marker testing. Respective rates of false positive test results among non-smokers, former smokers, and current smokers were: 16.3, 19.1, and 11.5% (p = 0.81) for urine cytology; 36.8, 42.0, and 32.7% for the uCyt+ test (p = 0.88); 18.0, 19.1, and 13.5% for FISH (p = 0.66); and 69.5, 71.6, and 71.2% for NMP22 (p = 0.67). Respective rates of false negatives among non-smokers, former smokers, and current smokers were: 31.4, 15.1, and 28.0% for cytology (p = 0.34); 21.4, 22.6, and 16.0% for uCyt+ test (p = 0.67); 24.3, 13.2, and 28.0% for FISH (p = 0.88); and 10.0, 18.9, and 8.0% for NMP22 (p = 0.80). CONCLUSIONS:Our results strongly suggest that smoking habits do not affect performance characteristics of urinary markers in the diagnostics of BC. 10.1007/s00432-018-2639-z
    Reflex fluorescence in situ hybridization assay for suspicious urinary cytology in patients with bladder cancer with negative surveillance cystoscopy. Kim Philip H,Sukhu Ranjit,Cordon Billy H,Sfakianos John P,Sjoberg Daniel D,Hakimi A Ari,Dalbagni Guido,Lin Oscar,Herr Harry W BJU international OBJECTIVE:To assess the ability of reflex UroVysion fluorescence in situ hybridization (FISH) testing to predict recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC) with suspicious cytology but negative cystoscopy. PATIENTS AND METHODS:Patients under NMIBC surveillance were followed with office cystoscopy and urinary cytology every 3-6 months. Between March 2007 and February 2012, 500 consecutive patients with suspicious cytology underwent reflex FISH analysis. Clinical and pathological data were reviewed retrospectively. Predictors for recurrence, progression and findings on subsequent cystoscopy (within 2-6 months after FISH) were evaluated using univariate and multivariate Cox regression. RESULTS:In all, 243 patients with suspicious cytology also had negative surveillance cystoscopy. Positive FISH was a significant predictor of recurrence (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.42-3.90, P = 0.001) in multivariate analysis and for progression (HR = 3.01, 95% CI: 1.10-8.21, P = 0.03) in univariate analysis, compared with negative FISH. However, positive FISH was not significantly associated with evidence of tumour on subsequent surveillance cystoscopy compared with negative FISH (odds ratio = 0.8, 95% CI: 0.26-2.74, P = 1). CONCLUSIONS:Positive FISH predicts recurrence and progression in patients under NMIBC surveillance with suspicious cytology but negative cystoscopy. However, there was no association between the FISH result and tumour recurrence in the immediate follow-up period. Reflex FISH testing for suspicious cytology might have limited ability to modify surveillance strategies in NMIBC. 10.1111/bju.12516
    The diagnostic accuracy of urine-based tests for bladder cancer varies greatly by patient. Gopalakrishna Ajay,Longo Thomas A,Fantony Joseph J,Owusu Richmond,Foo Wen-Chi,Dash Rajesh,Inman Brant A BMC urology BACKGROUND:Spectrum effects refer to the phenomenon that test performance varies across subgroups of a population. When spectrum effects occur during diagnostic testing for cancer, difficult patient misdiagnoses can occur. Our objective was to evaluate the effect of test indication, age, gender, race, and smoking status on the performance characteristics of two commonly used diagnostic tests for bladder cancer, urine cytology and fluorescence in situ hybridization (FISH). METHODS:We assessed all subjects who underwent cystoscopy, cytology, and FISH at our institution from 2003 to 2012. The standard diagnostic test performance metrics were calculated using marginal models to account for clustered/repeated measures within subjects. We calculated test performance for the overall cohort by test indication as well as by key patient variables: age, gender, race, and smoking status. RESULTS:A total of 4023 cystoscopy-cytology pairs and 1696 FISH-cystoscopy pairs were included in the analysis. In both FISH and cytology, increasing age, male gender, and history of smoking were associated with increased sensitivity and decreased specificity. FISH performance was most impacted by age, with an increase in sensitivity from 17 % at age 40 to 49 % at age 80. The same was true of cytology, with an increase in sensitivity from 50 % at age 40 to 67 % at age 80. Sensitivity of FISH was higher for a previous diagnosis of bladder cancer (46 %) than for hematuria (26 %). Test indication had no impact on the performance of cytology and race had no significant impact on the performance of either test. CONCLUSIONS:The diagnostic performance of urine cytology and FISH vary significantly according to the patient demographic in which they were tested. Hence, the reporting of spectrum effects in diagnostic tests should become part of standard practice. Patient-related factors must contextualize the clinicians' interpretation of test results and their decision-making. 10.1186/s12894-016-0147-5
    Automated quantification of FISH signals in urinary cells enables the assessment of chromosomal aberration patterns characteristic for bladder cancer. Köhler Christina U,Martin Laura,Bonberg Nadine,Behrens Thomas,Deix Thomas,Braun Katharina,Noldus Joachim,Jöckel Karl-Heinz,Erbel Raimund,Sommerer Florian,Tannapfel Andrea,Harth Volker,Käfferlein Heiko U,Brüning Thomas Biochemical and biophysical research communications Targeting the centromeres of chromosomes 3, 7, 17 (CEP3, 7, 17) and the 9p21-locus (LSI9p21) for diagnosing bladder cancer (BC) is time- and cost-intensive and requires a manual investigation of the sample by a well-trained investigator thus overall limiting its use in clinical diagnostics and large-scaled epidemiological studies. Here we introduce a new computer-assisted FISH spot analysis tool enabling an automated, objective and quantitative assessment of FISH patterns in the urinary sediment. Utilizing a controllable microscope workstation, the microscope software Scan^R was programmed to allow automatic batch-scanning of up to 32 samples and identifying quadruple FISH signals in DAPI-scanned nuclei of urinary sediments. The assay allowed a time- and cost-efficient, automated and objective assessment of CEP3, 7 and 17 FISH signals and facilitated the quantification of nuclei harboring specific FISH patterns in all cells of the urinary sediment. To explore the diagnostic capability of the developed tool, we analyzed the abundance of 51 different FISH patterns in a pilot set of urine specimens from 14 patients with BC and 21 population controls (PC). Herein, the results of the fully automated approach yielded a high degree of conformity when compared to those obtained by an expert-guided re-evaluation of archived scans. The best cancer-identifying pattern was characterized by a concurrent gain of CEP3, 7 and 17. Overall, our automated analysis refines current FISH protocols and encourages its use to establish reliable diagnostic cutoffs in future large-scale studies with well-characterized specimens-collectives. 10.1016/j.bbrc.2014.04.137
    The association of fish consumption with bladder cancer risk: a meta-analysis. Li Zhongyi,Yu Jianda,Miao Qilong,Sun Shuben,Sun Lingjun,Yang Houmen,Hou Liejun World journal of surgical oncology BACKGROUND:The association between fish consumption and risk of bladder cancer has not been established yet. The results from epidemiological studies are inconsistent. METHODS:We conducted a meta-analysis of cohort and case-control studies on the relationship between fish intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of relative risk associated to the highest versus the lowest category of fish intake using random effect models. Heterogeneity among studies was examined using Q and I2 statistics. Publication bias was assessed using the Begg's funnel plot. RESULTS:Five cohort and 9 case-control studies were eligible for inclusion. The combined relative risk showed that fish consumption was negatively, but not significantly, associated with a decreased risk of bladder cancer (relative risk, 0.86; 95% confidence interval, 0.61-1.12). In subgroup analyses, there was no evidence that study design, geographical region, case sample size, or exposure assessment substantially influenced the estimate of effects. CONCLUSION:The overall current literature on fish consumption and the risk of bladder cancer suggested no association. Because of the limited number of studies, further well-designed prospective studies are needed to explore the effect of fish on bladder cancer. 10.1186/1477-7819-9-107
    Association of chromosome 7 aneuploidy measured by fluorescence in situ hybridization assay with muscular invasion in bladder cancer. Diao Xiayao,Cai Jinhua,Zheng Junjiong,Kong Jianqiu,Wu Shaoxu,Yu Hao,Huang Hao,Xie Weibin,Chen Xiong,Huang Chengran,Huang Lifang,Qin Haide,Huang Jian,Lin Tianxin Cancer communications (London, England) BACKGROUND:The preoperative prediction of muscular invasion status is important for adequately treating bladder cancer (BC) but nevertheless, there are some existing dilemmas in the current preoperative diagnostic accuracy of BC with muscular invasion. Here, we investigated the potential association between the fluorescence in situ hybridization (FISH) assay and muscular invasion among patients with BC. A cytogenetic-clinical nomogram for the individualized preoperative differentiation of muscle-invasive BC (MIBC) from non-muscle-invasive BC (NMIBC) is also proposed. METHODS:All eligible BC patients were preoperatively tested using a FISH assay, which included 4 sites (chromosome-specific centromeric probe [CSP] 3, 7, and 17, and gene locus-specific probe [GLP]-p16 locus). The correlation between the FISH assay and BC muscular invasion was evaluated using the Chi-square tests. In the training set, univariate and multivariate logistic regression analyses were used to develop a cytogenetic-clinical nomogram for preoperative muscular invasion prediction. Then, we assessed the performance of the nomogram in the training set with respect to its discriminatory accuracy and calibration for predicting muscular invasion, and clinical usefulness, which were then validated in the validation set. Moreover, model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the individual variables incorporated in the nomogram. RESULTS:Muscular invasion was more prevalent in BC patients with positive CSP3, CSP7 and CSP17 status (OR [95% CI], 2.724 [1.555 to 4.774], P < 0.001; 3.406 [1.912 to 6.068], P < 0.001 and 2.483 [1.436 to 4.292], P = 0.001, respectively). Radiology-determined tumor size, radiology-determined clinical tumor stage and CSP7 status were identified as independent risk factors of BC muscular invasion by the multivariate regression analysis in the training set. Then, a cytogenetic-clinical nomogram incorporating these three independent risk factors was constructed and was observed to have satisfactory discrimination in the training (AUC 0.784; 95% CI: 0.715 to 0.853) and validation (AUC 0.743; 95% CI: 0.635 to 0.850) set. The decision curve analysis (DCA) indicated the clinical usefulness of our nomogram. In models comparison, using the receiver operator characteristic (ROC) analyses, the nomogram showed higher discriminatory accuracy than any variables incorporated in the nomogram alone and the DCAs also identified the nomogram as possessing the highest net benefits at wide range of threshold probabilities. CONCLUSION:CSP7 status was identified as an independent factor for predicting muscular invasion in BC patients and was successfully incorporated in a clinical nomogram combining the results of the FISH assay with clinical risk factors. 10.1002/cac2.12017