Non-invasive detection of bladder cancer using fluorescence in situ hybridization

T Okamura MD PhD^a, Y Umemoto MD^a, T Yasui MD PhD^b, K Kohri MD PhD^b

^aThe Urology Division, Meijo Hospital, Nagoya, Japan, ^bDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

AIM: 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 like p53 on chromosome 17, or p16 on chromosome 9, are thought to be important. In order to investigate whether such changes might be used as an alternative to invasive techniques for assessment of clinical bladder cancer cases, fluorescence in situ hybridization (FISH) was employed to analyze a series of cases. METHODS: A total of 40 patients with transitional cell carcinomas (stages Ta to T4, including CIS) were examined for abnormalities 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 with the same samples. One hundred cells were examined in each sample, and abnormality was concluded when more than 20% demonstrated polysomy. RESULTS: Seventeen of 41 samples (41.5%) were abnormal with regard to chromosome 9, and 17 of 42 (40.5%) for chromosome 17. Both were affected in 13 cases, of which eight were positive for urinary cytology and BTA. Monovariant analyses, performed with urinary cytology, BTA, tumor grade, stage, involvement of vessels, pattern of invasion, number of tumor, and prognosis as parameters, demonstrated significant influence of urinary cytology (p=0.0368 and p=0.0278 for chromosomes 9 and 17), BTA (p=0.0094 for 17), involvement of vessels (p=0.0262 for 17), pattern of invasion (p=0.0028 and p=0.0327 for 9 and 17), and grade (p=0.0213 and p=0.0174 for 9 and 17). All the other parameters also tended to be linked with the genetic abnormalities except for tumor number. CONCLUSIONS: Voided urine FISH is an effective non-invasive method for detection of bladder cancer and predicting prognosis when combined with urinary cytology and BTA.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).