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Abstract
Purpose
To evaluate the clinical utility of performing fluorescence in situ hybridization (FISH) in voided urine specimens for the diagnosis and surveillance of bladder cancer, we compared the results of FISH with the results of urine cytology.
Materials and Methods
Voided urine samples from 196 patients were obtained for performing FISH and urine cytology. The bladder cancer group consisted of 76 patients who had biopsy-proven bladder cancer, and the control group was 120 patients without bladder cancer. FISH was performed using the UroVysion kit. The sensitivity and specificity of FISH were determined and compared with that of urine cytology.
Results
The overall sensitivity for FISH was significantly higher than the corresponding value for urine cytology (50% vs. 23.7%, respectively, p= 0.001). The specificities for FISH and cytology were 97.5% and 99.2%, respectively. When analyzing the results concerning the T-category, the sensitivity of FISH and cytology was 22.9% and 8.6% for pTa, 79.2% and 45.8% for pT1, and 54.5% and 9.1% for pT2-4 tumors, respectively. Concerning the tumor grade, the sensitivity was 22.2% and 5.6% for G1, 48.5% and 24.2% for G2, 70.8% and 33.3% for G3 for FISH and cytology, respectively.
Conclusions
These findings show that the sensitivity of FISH for voided urine samples is higher than that of cytology, but the specificity was not significantly different. We recommend FISH as a useful diagnostic tool for patients who are suspected of having new bladder cancer and recurrent cancer, in combination with performing urine cytology.
REFERENCES
1.Ferlay J., Bray F., Pisani P., Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide, version 1.0. Lyon: IARC Press;2004.
2.Kim WJ., Chung JI., Hong JH., Kim CS., Jung SI., Yoon DK. Epidemiological study for urologic cancer in Korea (1998-2002). Korean J Urol. 2004. 45:1081–8.
3.Ministry of Health and Welfare Republic of Korea. 2002 Annual report of the Korea central cancer registry (based on registered data from 139 hospitals). Korea central cancer registry. 2003.
4.Lee R., Droller MJ. The natural history of bladder cancer. Implications for therapy. Urol Clin North Am. 2000. 27:1–13.
5.Almallah YZ., Rennie CD., Stone J., Lancashire MJ. Urinary tract infection and patient satisfaction after flexible cystoscopy and urodynamic evaluation. Urology. 2000. 56:37–9.
6.Sherman AB., Koss LG., Adams SE. Interobserver and intraobserver differences in the diagnosis of urothelial cells. Comparison with classification by computer. Anal Quant Cytol. 1984. 6:112–20.
7.van Rhijn BW., van der Poel HG., van der Kwast TH. Urine markers for bladder cancer surveillance: a systematic review. Eur Urol. 2005. 47:736–48.
8.Jones JS. DNA-based molecular cytology for bladder cancer surveillance. Urology. 2006. 67(3 Suppl 1):35–45.
9.Sarosdy MF., Schellhammer P., Bokinsky G., Kahn P., Chao R., Yore L, et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer. J Urol. 2002. 168:1950–4.
10.Choi YD., Cho NH., Chang SY., Rha SY., Chung HC., Park KM. Comparison of the efficacy of urine cytology and fluorescence in situ hybridization (FISH) for the detection of bladder urothelial carcinoma. Korean J Urol. 2004. 45:410–5.
11.Placer J., Espinet B., Salido M., Sole F., Gelabert-Mas A. Clinical utility of a multiprobe FISH assay in voided urine specimens for the detection of bladder cancer and its recurrences, compared with urinary cytology. Eur Urol. 2002. 42:547–52.
12.Friedrich MG., Toma MI., Hellstern A., Pantel K., Weisenberger DJ., Noldus J, et al. Comparison of multitarget fluorescence in situ hybridization in urine with other noninvasive tests for detecting bladder cancer. BJU Int. 2003. 92:911–4.
13.Bubendorf L., Grilli B., Sauter G., Mihatsch MJ., Gasser TC., Dalquen P. Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol. 2001. 116:79–86.
14.Skacel M., Fahmy M., Brainard JA., Pettay JD., Biscotti CV., Liou LS, et al. Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. J Urol. 2003. 169:2101–5.
15.Junker K., Fritsch T., Hartmann A., Schulze W., Schubert J. Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for the detection of bladder cancer. Cytogenet Genome Res. 2006. 114:279–83.
16.Boman H., Hedelin H., Holmang S. Four bladder tumor markers have a disappointingly low sensitivity for small size and low grade recurrence. J Urol. 2002. 167:80–3.
17.Schrag D., Hsieh LJ., Rabbani F., Bach PB., Herr H., Begg CB. Adherence to surveillance among patients with superficial bladder cancer. J Natl Cancer Inst. 2003. 95:588–97.
18.Tsukamoto M., Matsuyama H., Oba K., Yoshihiro S., Takahashi M., Naito K. Numerical aberrations of chromosome 9 in bladder cancer. A possible prognostic marker for early tumor recurrence. Cancer Genet Cytogenet. 2002. 134:41–5.
19.Kruger S., Mess F., Bohle A., Feller AC. Numerical aberrations of chromosome 17 and the 9p21 locus are independent predictors of tumor recurrence in non-invasive transitional cell carcinoma of the urinary bladder. Int J Oncol. 2003. 23:41–8.
20.Bollmann M., Heller H., Bankfalvi A., Griefingholt H., Bollmann R. Quantitative molecular urinary cytology by fluorescence in situ hybridization: a tool for tailoring surveillance of patients with superficial bladder cancer? BJU Int. 2005. 95:1219–25.
Table 1.
The overall sensitivity and specificity of FISH and cytology
| FISH | Cytology | p-value | |
|---|---|---|---|
| Sensitivity (No./Total No.) | 50% (38/76) | 23.7% (18/76) | 0.001 |
| Specificity (No./Total No.) | 97.5% (117/120) | 99.2% (119/120) | 0.622 |
Table 2.
The sensitivity by stage and grade
Table 3.
The concordance between FISH and cytology for the bladder cancer group
| FISH ? | Cytology, n (%) | |
|---|---|---|
| Positive or suggestive | Negative or atypical | |
| Positive | 15 (20) | 23 (30) |
| Negative | 3 (4) | 35 (46) |
Table 4.
Adjustment of the cutoff values for FISH positive
| Criteria* | % Sensitivity (n) | % Specificity (n) |
|---|---|---|
| (1) | 50.0 (38) | 97.5 (117) |
| (2) | 56.6 (43) | 95.8 (115) |
| (3) | 60.5 (46) | 90.8 (109)† |
| (4) | 64.5 (49) | 85.8 (103)† |
FISH: fluorescence in situ hybridization, *: All the criteria were counted for 20 morphologically abnormal cells by two observers for each probe. (1): multiple chromosomal gains in more than 4 cells (more than one of the 3 probes: CEP3, CEP7, CEP17) or homozygous loss of p16 in more than 12 cells, (2): gains in more than 4 cells (more than one of the 3 probes) or gains in more than 8 cells (one probe or more) or loss of p16 in more than 8 cells, (3): gains in more than 2 cells (one probe or more) or loss of p16 in more than 1 cell, (4): gains of any probe or loss of p16 in any cell
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