A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma.

PURPOSE We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.

[1]  P. Schellhammer,et al.  Improved detection of recurrent bladder cancer using the Bard BTA stat Test. , 1998, Urology.

[2]  L. Koss,et al.  Diagnostic value of cytology of voided urine. , 1985, Acta Cytologica.

[3]  M. Marberger,et al.  Can urine bound diagnostic tests replace cystoscopy in the management of bladder cancer? , 1998, The Journal of urology.

[4]  A. Sandberg,et al.  Review of chromosome studies in urological tumors. II. Cytogenetics and molecular genetics of bladder cancer. , 1994, The Journal of urology.

[5]  F. Ramaekers,et al.  Detection of Genetic Aberrations in Bladder Cancer Using in Situ Hybridization a , 1993, Annals of the New York Academy of Sciences.

[6]  P. Wingo,et al.  Cancer statistics, 1997 , 1997, CA: a cancer journal for clinicians.

[7]  M. Slovak,et al.  Toward the validation of aneusomy detection by fluorescence in situ hybridization in bladder cancer: comparative analysis with cytology, cytogenetics, and clinical features predicts recurrence and defines clinical testing limitations. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  G. Farrow,et al.  Urine cytology of transitional cell neoplasms. , 1979, The Urologic clinics of North America.

[9]  J. Hofbauer,et al.  Fluorescence in situ hybridization identifies more aggressive types of primarily noninvasive (stage pTa) bladder cancer. , 1997, The Journal of urology.

[10]  L. Koss.  Tumors of the urinary bladder , 1979 .

[11]  E. Meuleman,et al.  Diagnostic efficacy of the combination of urine cytology, urine analysis and history in the follow-up of bladder carcinoma. , 1988, British journal of urology.

[12]  J. Bacus,et al.  Cytology, flow cytometry, image analysis, and interphase cytogenetics by fluorescence in situ hybridization in the diagnosis of transitional cell carcinoma in bladder washes: A comparative study , 1995, Diagnostic cytopathology.

[13]  D. Grignon,et al.  Matrix metalloproteinase-9 expression in bladder washes from bladder cancer patients predicts pathological stage and grade. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  H. Moch,et al.  Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization. , 1997, Cancer research.

[15]  P. Carroll,et al.  Frequent homozygous deletion of cyclin‐dependent kinase inhibitor 2 (MTS1, p16) in superficial bladder cancer detected by fluorescence in situ hybridization , 1997, Genes, chromosomes & cancer.

[16]  M. Droller,et al.  Bladder cancer: State‐of‐the‐art care , 1998, CA: a cancer journal for clinicians.

[17]  K. Rieger,et al.  Identification of H-ras mutations in urine sediments complements cytology in the detection of bladder tumors. , 1995, Journal of the National Cancer Institute.

[18]  A. Peier,et al.  A new approach in the diagnosis and follow-up of bladder cancer. FISH analysis of urine, bladder washings, and tumors. , 1993, Cancer genetics and cytogenetics.

[19]  G. Hannon,et al.  Deletion of the p16 and p15 genes in human bladder tumors. , 1995, Journal of the National Cancer Institute.

[20]  T. Colby,et al.  Reliability of urinary cytodiagnosis in urothelial neoplasms , 1985, Cancer.

[21]  W. Ellis,et al.  Clinical evaluation of the BTA TRAK assay and comparison to voided urine cytology and the Bard BTA test in patients with recurrent bladder tumors. The Multi Center Study Group. , 1997, Urology.

[22]  H. Moch,et al.  Chromosomal imbalances in noninvasive papillary bladder neoplasms (pTa). , 1999, Cancer research.

[23]  O. Yoshida,et al.  Detection of telomerase activity in exfoliated cells in urine from patients with bladder cancer. , 1997, Journal of the National Cancer Institute.

[24]  Jeffrey K. Cohen,et al.  Origins and clinical implications of aneuploidy in early bladder cancer. , 1995, Cytometry.

[25]  D. Lamm.  Diagnosis and treatment of bladder cancer , 1992, Anti-cancer drugs.

[26]  H. G. van der Poel,et al.  Bladder wash cytology, quantitative cytology, and the qualitative BTA test in patients with superficial bladder cancer. , 1998, Urology.

[27]  G. Farrow.  Pathology of carcinoma in situ of the urinary bladder and related lesions , 1992, Journal of cellular biochemistry. Supplement.

[28]  B. Lamy,et al.  Clinical evaluation of cell deoxyribonucleic acid content measured by flow cytometry in bladder cancer. , 1996, The Journal of urology.

[29]  H. Moch,et al.  Polysomies but not Y chromosome losses have prognostic significance in pTa/pT1 urinary bladder cancer. , 1999, Human pathology.

[30]  K. Junker,et al.  Interphase cytogenetic diagnosis of bladder cancer on cells from urine and bladder washing. , 1999, International journal of oncology.

[31]  M. Knowles,et al.  Initiation of bladder cancer may involve deletion of a tumour-suppressor gene on chromosome 9. , 1993, Oncogene.

[32]  P. Schellhammer,et al.  Results of a multicenter trial using the BTA test to monitor for and diagnose recurrent bladder cancer. , 1995, The Journal of urology.

[33]  D J O'Kane,et al.  Comparison of screening methods in the detection of bladder cancer. , 1999, The Journal of urology.

[34]  D. Lamm,et al.  A multicenter trial evaluation of the fibrin/fibrinogen degradation products test for detection and monitoring of bladder cancer. , 1997, Journal of Urology.

[35]  B. Liu,et al.  Sensitivity and specificity of NMP-22, telomerase, and BTA in the detection of human bladder cancer. , 1999, Urology.

[36]  J. Epstein,et al.  Partial allelotype of carcinoma in situ of the human bladder. , 1995, Cancer research.

[37]  L. Wheeless,et al.  Bladder irrigation specimens assayed by fluorescence in situ hybridization to interphase nuclei. , 1994, Cytometry.

[38]  S. Zeger,et al.  Longitudinal data analysis using generalized linear models , 1986 .

[39]  H. Leyh,et al.  Bard BTA test compared with voided urine cytology in the diagnosis of recurrent bladder cancer. , 1997, European urology.

[40]  M. Droller,et al.  Detecting human bladder carcinoma cells in voided urine samples by assaying for the presence of telomerase activity , 1998, Cancer.

[41]  E. Messing,et al.  Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. , 1996, The Journal of urology.

[42]  B. M. Brown,et al.  Practical Non-Parametric Statistics. , 1981 .

[43]  H. Zincke,et al.  Review of Mayo Clinic experience with carcinoma in situ. , 1986, Urology.

[44]  H. Herr.  Carcinoma in situ of the bladder. , 1983, Seminars in urology.

[45]  S. Kagawa,et al.  Semi-quantitative analysis of telomerase activity in exfoliated human urothelial cells and bladder transitional cell carcinoma. , 1998, British journal of urology.

[46]  R. Simak,et al.  The clinical value of urinary cytology: 12 years of experience with 615 patients. , 1995, Journal of clinical pathology.

[47]  G. Farrow.  Urine cytology in the detection of bladder cancer: a critical approach. , 1990, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[48]  C. Sternberg,et al.  Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer. , 1999, Clinical chemistry.

[49]  L. Koss.  Bladder caner from a perspective of 40 years , 1992, Journal of cellular biochemistry. Supplement.

[50]  K. Sasaki,et al.  Intratumoral heterogeneity in DNA ploidy of bladder carcinomas. , 1992, Oncology.

[51]  D. Sidransky,et al.  Evidence for two bladder cancer suppressor loci on human chromosome 9. , 1993, Cancer research.

[52]  H. G. van der Poel,et al.  The Bard® BTA Test: Its Mode of Action, Sensitivity and Specificity, Compared to Cytology of Voided Urine, in the Diagnosis of Superficial Bladder Cancer , 1998, European Urology.

[53]  R. Cote,et al.  Two molecular pathways to transitional cell carcinoma of the bladder. , 1994, Cancer research.

[54]  K. McVary,et al.  Interphase cytogenetics as an adjunct in the cytodiagnosis of urinary bladder carcinoma. A comparative study of cytology, flow cytometry and interphase cytogenetics in bladder washes. , 1994, Analytical and quantitative cytology and histology.

[55]  H. Miyake,et al.  Urinary cytology and competitive reverse transcriptase-polymerase chain reaction analysis of a specific CD44 variant to detect and monitor bladder cancer. , 1998, The Journal of urology.