Noninvasive detection of alterations in chromosome numbers in urinary bladder cancer cells, using fluorescence in situ hybridization.

Background: Bladder cancers have a high potential for recurrence and sometimes become invasive even in superficial cases. In this process, gene mutations in tumor suppressor genes such as p53, on chromosome 17, or p16, on chromosome 9, are thought to be important. In order to investigate whether the detection of alterations in chromosome number might be used as an alternative to invasive techniques for the assessment of clinical bladder cancer, fluorescence in situ hybridization (FISH) was employed to analyze chromosome numbers in a series of patients.

Methods: A total of 40 patients with transitional cell carcinomas (stages Ta to T4, including carcinoma in situ [CIS]) were examined for abnormal numbers of chromosomes 9 and 17, by FISH, using 41 and 42 samples of voided urine, respectively. Tumor grades were as follows: G1:G2:G3 = 4:21:17. Urinary cytology and presence of bladder tumor antigen (BTA) were also checked in the same samples. One hundred cells were examined in each sample, and abnormality was concluded to be present when more than 20% of cells demonstrated polysomy (defined as three or more chromosomes).

Results: Seventeen of 41 samples (41.5%) were abnormal with regard to chromosome 9, and 17 of 42 (40.5%) were abnormal for chromosome 17. Both chromosomes were affected in 13 cases, of which 8 were positive for urinary cytology and BTA. Univariate analysis, performed with urinary cytology, BTA, tumor grade, tumor stage, involvement of vessels, pattern of invasion, number of tumors, and prognosis as parameters, demonstrated a significant influence of urinary cytology (P = 0.0368 and P = 0.0278 for chromosomes 9 and 17, respectively), BTA (P = 0.0094 for chromosome 17), involvement of vessels (P = 0.0262 for chromosome 17), pattern of invasion (P = 0.0028 and P = 0.0327 for chromosomes 9 and 17), grade (P = 0.0213 and P = 0.0174 for chromosomes 9 and 17), and stage (P = 0.0457 for chromosome 17). All the other parameters also tended to be linked with the changes in chromosomes, except for tumor number. Multivariate analysis demonstrated significant differences for tumor grade (P = 0.0166) and pattern of invasion (P = 0.0006) for chromosome 9.

Conclusion: Voided-urine FISH is an effective noninvasive method for the detection of altered chromosome numbers in bladder cancer cells, and may provide an indication of tumor progression when combined with urinary cytology and BTA.