Korean J Urol.  2009 Jan;50(1):6-11. 10.4111/kju.2009.50.1.6.

Comparison of the Efficacy of Urine Cytology, Nuclear Matrix Protein 22 (NMP22), and Fluorescence in Situ Hybridization (FISH) for the Diagnosis of Bladder Cancer

• Kim WT
• Park K
• Cho NH
• Ham WS
• Lee JS
• Ju HJ
• Kwon YU
• Choi YD

• KMID: 2140106
• DOI: http://doi.org/10.4111/kju.2009.50.1.6

Abstract

PURPOSE: We compared the efficacy of urine cytology, nuclear matrix protein 22 (NMP22), and fluorescence in situ hybridization (FISH) for the detection of bladder cancer.
MATERIALS AND METHODS
Washing urine samples from 156 patients were evaluated for the detection of bladder cancer. Patients were divided into 3 groups. Group 1 was 106 patients with bladder cancer, group 2 was 30 patients with benign prostatic hyperplasia who underwent transurethral resection of the prostate without bladder cancer, and group 3 had gross hematuria without bladder cancer. The sensitivity and specificity of cytology, NMP22, and FISH were compared. NMP22 positivity was defined as > or =10U/ml. FISH was done with the UroVysion(R) system and FISH positivity was defined as > or =2 abnormal urothelial cells with an abnormal signal from any out of 4 probes.
RESULTS
The overall sensitivity of urine cytology, NMP22, and FISH was 60.4%, 75.5%, and 84.9%, respectively (p<0.001). The overall specificity of cytology, NMP22, and FISH was 96.7%, 83.3%, and 93.3%, respectively (p=0.168). In group 3, the false-positive rates of cytology, NMP22, and FISH were 20.0%, 55.0%, and 10.0%, respectively. In these patients with gross hematuria, the false-positive rate with NMP22 was significantly higher than with cytology or FISH (p=0.004). The sensitivity of cytology, NMP22, and FISH in low-grade bladder cancer patients was 25.9%, 51.9%, and 77.8%, respectively, and that in pTa-1 bladder cancer patients was 40.6%, 65.6%, and 78.1%, respectively. In low-grade or in pTa-1 patients, the sensitivity of the three diagnostic tools was significantly different (low grade; p<0.001, pTa-1; p<0.001).
CONCLUSIONS
FISH is more sensitive in low-grade bladder cancer than is urine cytology and can be used as a diagnostic tool for the detection of primary and recurrent bladder cancer. NMP22 was affected by gross hematuria and thus has limitations for screening of bladder cancer. However, it can be used to follow-up bladder cancer.

Keyword

Transitional cell carcinoma; In situ hybridization, fluorescence; Nuclear matrix protein 22

MeSH Terms

Carcinoma, Transitional Cell
Fluorescence
Hematuria
Humans
In Situ Hybridization
In Situ Hybridization, Fluorescence
Mass Screening
Nuclear Matrix
Nuclear Proteins
Prostate
Prostatic Hyperplasia
Sensitivity and Specificity
Urinary Bladder
Urinary Bladder Neoplasms
Nuclear Proteins

Reference

1. 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.

2. Dalbagni G, Herr HW. Current use and questions concerning intravesical bladder cancer group for superficial bladder cancer. Urol Clin North Am. 2000. 27:137–146.

3. Donat SM. Evaluation and follow-up strategies for superficial bladder cancer. Urol Clin North Am. 2003. 30:765–776.

4. Lee R, Droller MJ. The natural history of bladder cancer. Implications for therapy. Urol Clin North Am. 2000. 27:1–13.

5. Soloway MS. Overview of treatment of superficial bladder cancer. Urology. 1985. 26:4 Suppl. 18–26.

6. Halling KC, King W, Sokolova IA, Meyer RG, Burkhardt HM, Halling AC, et al. A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. J Urol. 2000. 164:1768–1775.

7. Grossman HB, Messing E, Soloway M, Tomera K, Katz G, Berger Y, et al. Detection of bladder cancer using a point-of-care proteomic assay. JAMA. 2005. 293:810–816.

8. Lübbe L, Nowack R, May M, Ullmann K, Gunia S, Kaufmann O, et al. FISH--a new noninvasive method for the diagnosis of urinary bladder carcinomas. Clin Lab. 2004. 50:395–402.

9. Menendez V, Filella X, Alcover JA, Molina R, Mallafre JM, Ballesta AM, et al. Usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for transitional cell carcinoma of the bladder. Anticancer Res. 2000. 20:1169–1172.

10. Epstein JI, Amin MB, Reuter VR, Mostofi FK. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol. 1998. 22:1435–1448.

11. Greene F, Page L, Fleming L, Fritz AG, Balch CM, Haller DG. AJCC Cancer Staging Manual. 2002. 6th ed. New York: Springer Verlag.

12. Keesee SK, Meneghini MD, Szaro RP, Wu YJ. Nuclear matrix proteins in human colon cancer. Proc Natl Acad Sci U S A. 1994. 91:1913–1916.

13. Di Carlo A, Terracciano D, Mariano A, Oliva A, D'Armiento M, Macchia V. Role of cytokeratins, nuclear matrix proteins, Lewis antigen and epidermal growth factor receptor in human bladder tumors. Int J Oncol. 2003. 23:757–762.

14. Sharma S, Zippe CD, Pandrangi L, Nelson D, Agarwal A. Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat. J Urol. 1999. 162:53–57.

15. Ponsky LE, Sharma S, Pandrangi L, Kedia S, Nelson D, Agarwal A, et al. Screening and monitoring for bladder cancer: refining the use of NMP22. J Urol. 2001. 166:75–78.

16. Gibas Z, Prout GR Jr, Connolly JG, Pontes JE, Sandberg AA. Nonrandom chromosomal changes in transitional cell carcinoma of the bladder. Cancer Res. 1984. 44:1257–1264.

17. Vanni R, Scarpa RM, Nieddu M, Usai E. Cytogenetic investigation on 30 bladder carcinomas. Cancer Genet Cytogenet. 1988. 30:35–42.

18. Meloni AM, Peier AM, Haddad FS, Powell IJ, Block AW, Huben RP, et al. 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.

19. 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. 169:2101–2105.

20. Choi YD, Cho NH, Chang SY, Rha SY, Chung HC, Park K. Comparison of the efficacy of urine cytology and fluorescence in situ hybridization (FISH) for the detection of bladder urothelial carcinoma. Korean J Urol. 2004. 45:410–415.

21. Kim JY, Kim SH, Choi HY, Lee HM. Clinical utility of fluorescence in situ hybridization for voided urine for the diagnosis and surveillance of bladder cancer. Korean J Urol. 2008. 49:307–312.

22. 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. 168:1950–1954.

23. Pycha A, Lodde M, Comploj E, Negri G, Egarter-Vigl E, Vittadello F, et al. Intermediate-risk urothelial carcinoma: an unresolved problem? Urology. 2004. 63:472–475.

24. Kim JS, Lee HM, Lee KH. The significance of urinary nuclear matrix protein (NMP) as a Marker for transitional cell carcinoma of the bladder. Korean J Urol. 1997. 38:259–262.

25. Kim HY, Chang SG, Kim JI. The significance of urinary NMP22 in patients with bladder tumor as a diagnostic test. Korean J Urol. 1998. 39:450–453.

26. Park JO, Moon DG, Cheon J, Kim JJ, Yoon DK. Urinary NMP (nuclear matrix protein) 22 in screening and post-treatment follow-up of bladder cancer. Korean J Urol. 1999. 40:551–556.

27. Kwon DH, Hong SJ. The clinical utility of BTA TRAK, BTA stat, NMP22 and urine cytology in the diagnosis of bladder cancer: a comparative study. Korean J Urol. 2003. 44:721–726.