Objective: Previous studies on touch biopsy specimens have determined numerical or structural changes involving many different chromosomes in bladder cancer. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) assay in bladder washings as an objective technique to detect chromosomal numerical aberrations in bladder cancer. The main advantages of bladder washings are that they can be easily collected during the clinical follow–up of patients with superficial bladder cancer and they do not contain so many degenerate cells as urine samples. Methods: We collected specimens from 25 patients who underwent transurethral resection of bladder tumors. Double target FISH assays with centromeric labeled probes for chromosomes 7, 8, 9 and 11 were used on the bladder washings and on the touch biopsy slides. The results were compared to flow cytometry and tumor grade and stage. Results: We found monosomy 9 and trisomy 7, 8, 9 and 11 in 28, 32, 36, 28 and 25% respectively of the patients. FISH analysis of bladder washing versus touch biopsy specimens were concordant in approximately 90% of the slides. Total DNA aneuploidy correlated well with numerical aberrations of chromosomes 7, 8 and 11, but not with chromosome 9. Conclusion: Although better hybridization efficiency was obtained on touch biopsy slides, the results in bladder washings were in high concordance. FISH analysis on bladder washing samples may become a simple tool to improve the accuracy of cytology.

Cairns P, Shaw ME, Knowles MA: Initiation of bladder cancer may involve deletion of a tumour suppressor gene on chromosome 9. Oncogene 1993;8:1083–1085.
Reznikoff CA, Belair CD, Yeager TR, Savelieva E, Blelloch RH, Puthenveettil JA, Cuthill S: A molecular genetic model of human bladder cancer pathogenesis. Semin Oncol 1996;23: 571–584.
Saran KK, Gould D, Godec JC, Verma RS: Genetics of bladder cancer. J Mol Med 1996;74: 441–445.
Hopman AH, Moesker O, Smeets AW, Pauwels RP, Vooijs GP, Ramaekers FC: Numerical chromosome 1, 7, 9, and 11 aberrations in bladder cancer detected by in situ hybridization. Cancer Res 1991;51:644–651.
Matsuyama H, Bergerheim US, Nilsson I, Pan Y, Skoog L, Tribukait B, Ekman P: Nonrandom numerical aberrations of chromosomes 7, 9, and 10 in DNA diploid bladder cancer. Cancer Genet Cytogenet 1994;77:118–124.
Meloni AM, Peier AM, Haddad FS, Powell IJ, Block AW, Huben RP, Todd I, Potter W, Sandberg AA: A new approach in the diagnosis and follow–up of bladder cancer. FISH analysis of urine, bladder washings, and tumors. Cancer Genet Cytogenet 1993;71:105–118.
Wheeless LL, Reeder JE, Han R, O’Connell MJ, Frank IN, Cockett AT, Hopman AH: Bladder irrigation specimens assayed by fluorescence in situ hybridization to interphase nuclei. Cytometry 1994;17:319–326.
Lichter P, Cremer T, Borden J, Manuelidis L, Ward DC: Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet 1988; 80:224–234.
Matsuyama H, Pan Y, Skoog L, Tribukait B, Naito K, Ekman P, Lichter P, Bergerheim US: Deletion mapping of chromosome 8p in prostate cancer by fluorescence in situ hybridization. Oncogene 1994;9:3071–3076.
Castro J, Heiden T, Wang N, Tribukait B: Preparation of cell nuclei from fresh tissues for high quality DNA flow cytometry. Cytometry 1993;14:793–804.
Norming U, Nyman CR, Tribukait B: Comparative histopathology and deoxyribonucleic acid flow cytometry of random mucosal biopsies in untreated bladder carcinoma. J Urol 1991;145:1164–1168.
Habuchi T, Devlin J, Elder PA, Knowles MA: Detailed deletion mapping of chromosome 9q in bladder cancer: Evidence for two tumour suppressor loci. Oncogene 1995;11:1671– 1674.
Sauter G, Moch H, Carroll P, Kerschmann R, Mihatsch MJ, Waldman FM: Chromosome 9 loss detected by fluorescence in situ hybridization in bladder cancer. Int J Cancer 1995;64: 99–103.
Smeets W, Schapers R, Hopman A, Pauwels R, Ramaekers F: Concordance between karyotyping and in situ hybridization procedures in the detection of monosomy 9 in bladder cancer. Cancer Genet Cytogenet 1993;71:97–99.
Keen AJ, Knowles MA: Definitiion of two regions of deletion on chromosome 9 in carcinoma of the bladder. Oncogene 1994;9:2083– 2088.
Miyao N, Tsai YC, Lerner SP, Olumi AF, Spruck CH, Gonzalez Zulueta M, Nichols PW, Skinner DG, Jones PA: Role of chromosome 9 in human bladder cancer. Cancer Res 1993; 53:4066–4070.
Waldman FM, Carroll PR, Kerschmann R, Cohen MB, Field FG, Mayall BH: Centromeric copy number of chromosome 7 is strongly correlated with tumor grade and labeling index in human bladder cancer. Cancer Res 1991;51: 3807–3813.
Knowles MA, Shaw ME, Proctor AJ: Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms. Oncogene 1993;8:1357–1364.
Sauter G, Carroll P, Moch H, Kallioniemi A, Kerschmann R, Narayan P, Mihatsch MJ, Waldman FM: c–myc copy number gains in bladder cancer detected by fluorescence in situ hybridization. Am J Pathol 1995;146:1131– 1139.
Bergerheim US, Kunimi K, Collins VP, Ekman P: Deletion mapping of chromosomes 8, 10, and 16 in human prostatic carcinoma. Genes Chromosom Cancer 1991;3:215–220.
Voorter CE, Ummelen MI, Ramaekers FS, Hopman AH: Loss of chromosome 11 and11 p/q imbalances in bladder cancer detected by fluorescence in situ hybridization. Int J Cancer 1996;65:301–307.
Moore LE, Titenko Holland N, Smith MT: Use of fluorescence in situ hybridization to detect chromosome–specific changes in exfoliated human bladder and oral mucosa cells. Environ Mol Mutagen 1993;22:130–137.
Mao L, Shoenberg MP, Scicchitano M, Erozan YS, Merlo A, Schwab D, Sidransky D: Molecular detection of primary bladder cancer by microsatellite analysis. Science 1996;271:659– 662.
Lee SE, Kim YK: Flow cytometric determination of the DNA content in transitional cell carcinoma of the bladder: Predictability of ploidy with regard to pelvic lymph node metastasis. Int J Urol 1994;1:232–236.
Gustafson H, Tribukait B: Characterization of bladder carcinomas by flow DNA analysis. Eur Urol 1985;11:410–417.
Muller Ladner U, Kriegsmann J, Gay RE, Gay S: A one–day double–labelling technique for tissue specimens: Immunogold–silver staining for in situ hybridization combined with alkaline phosphatase–anti–alkaline phosphatase (APAPP) immunohistochemistry for antigens. Histochem J 1996;28:133–134.
Tao Q, Srivastava G, Loke SL, Chan EY, Ho F: Improved double immunohistochemical staining method for cryostat and paraffin wax sections, combining alkaline phosphatase antialkaline phosphatase and indirect immunoflu– orescence. J Clin Pathol 1994;47:597–600.
Speicher MR, Gwyn Ballard S, Ward DC: Karyotyping human chromosomes by combinatorial multifluor FISH. Nat Genet 1996;12: 368–375.
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