Bladder carcinoma is the foremost oncologic problem among males in Egypt. Here, we evaluated the possible diagnostic value of the urinary Nuclear Matrix Protein-22 “NMP-22” and Telomerase Reverse Transcriptase “hTERT” among histological subtypes of bladder cancer. 120 males with non-muscle invasive bladder cancer, 21 non malignant bladder conditions and 21 healthy volunteers were included in this study. Estimation of hTERT and NMP-22 was done by PCR-ELISA and ELISA, respectively, from voided urine and results were compared to those of urine cytology. Results showed that urinary hTERT and NMP-22 were significantly higher in all cancer patients compared to control group. NMP-22 was able to discriminate between transitional cell bladder carcinoma “TCC” patients and squamous cell bladder carcinoma “SqCC” ones. Both markers succeded to discriminate between some transitional cell bladder carcinoma grades. Additionally, hTERT discriminated between some Tumor stages in both TCC and SqCC. Our results demonstrated that urinary hTERT and NMP-22 could be efficient urinary markers for the differential diagnosis of bladder cancer.
KeywordsBladder CancerUrinary MarkersNMP-22hTERT
C. T. Nguyen and J. S. Jones, “Defining the Role Of NMP-22 In Bladder Cancer Surveillance,” World Journal of Urology, Vol. 26, No. 1, 2008, pp. 51-58. doi:10.1007/s00345-007-0226-z
Statistical Report For NCI of Egypt, 2004. http://www.nci. edu.eg/
N. G. El-Mawla, M. N. El-Bolkainy and H. M. Khaled, “Bladder Cancer in Africa: Update,” Seminars in Oncology, Vol. 28, No. 2, 2001, pp. 174-178. doi:10.1053/sonc.2001.21961
M. Muscheck, H. Abol-Enein, K. Chew, D. Moore , V. Bhargava, M. A. Ghoneim, P. R. Carroll and F. M. Waldman, “Comparison of Genetic Changes in Schistosome-Related Bladder Transitional and Squamous Bladder Cancers Using Comparative Genomic Hybridization,” Carcinogenesis, Vol. 21, No. 9, 2000, pp. 1721-1726. doi:10.1093/carcin/21.9.1721
W. Zhao, X. S. Wang, H. T. Niu, L. L. Wang, B. M. Han and S. J. Xia, “Clinical Relevance of Heparanase Mrna Expression in Bladder Cancer and Its Usefulness as a Detection Marker in Voided Urine,” Molecular Medicine, Vol. 2, No. 2, 2009, pp. 327-331.
M. S. Zaghloul, “Adjuvant and Neoadjuvant Radiotherapy for Bladder Cancer: Revisited,” Future Oncology, Vol. 6, No.7, 2010, pp. 1177-1191. doi:10.2217/fon.10.82
P. Dey, “Urinary Markers of Bladder Carcinoma,” Cli- nica Chimica Acta, Vol. 340, No. 1-2, 2004, pp. 57-65. doi:10.1016/j.cccn.2003.11.008
R. Berezney, “The Nuclear Matrix: A Heuristic Model for Investigating Genomic Organization and Function in the Cell Nucleus,” Journal of Cellular Biochemistry, Vol. 47, No. 2, 1991, pp. 110-123. doi:10.1002/jcb.240470204
R. H. Getzenberg, B. R. Konety, T. A. Oeler, M. M. Quigley, A. Hakam, M. J. Becich and R. R. Bahnson, “Bladder Cancer Associated Nuclear Matrix Proteins,” Cancer Research, Vol. 56, No. 7, 1996, pp. 1690-1694.
N. W. Kim, M. A. Piatyszek, K. R. Prowse, C. B. Harley, M. D. West, P. L. Ho, G. M. Coviello, W. E. Wright, S. L. Weinrich and J. W. Shay, “Specific Association of Human Telomerase Activity with Immortal Cells and Cancer,” Science, Vol. 266, No. 5193, 1994, pp. 2011-2015. doi:10.1126/science.7605428
E. H. Blackburn, “Telomeres and Telomerase: Their Mechanisms of Action and Effects of Altering Their Functions,” FEBS Letters, Vol. 579, No. 4, 2005, pp. 859-862. doi:10.1016/j.febslet.2004.11.036
C. J. Cairney and W. N. Keth, “Telomerase Redefined: Integrated Regulation of Htr and Htert for Telomere Maintenance and Telomerase Activity,” Biochimie, Vol. 90, No. 1, 2008, pp. 13-23. doi:10.1016/j.biochi.2007.07.025
M. L. Quek, K. Sanderson, S. Daneshmand and J. P. Stein, “New Molecular Markers for Bladder Cancer Detection,” Current Opinion in Urology, Vol. 14, No. 5, 2004, pp. 259-264. doi:10.1097/00042307-200409000-00003
R. Reed, D. Holmes, J. Weyers and A. Jones, “Choosing and Using Statistical Tests,” Practical Skills in Biomolecular Sciences, 2nd Edition, Pearson Education, 2003, p. 485.
N. G. El-Mawla, M. N. El-Bolkainy and H. M. Khaled, “Bladder Cancer in Africa: Update,” Seminars in Oncology, Vol. 28, No. 2, 2001, pp. 174-178. doi:10.1053/sonc.2001.21961
H. M. Khaled, I. Abdel-Salam, M. Abdel-Gawad, A. Metwally, S. El-Demerdash, M. El-Didi, A. Morsi and L. Ishak, “Evaluation of The BTA Tests for the Detection of Bilharzial Related Bladder Cancer: The Cairo Experience,” European Urology, Vol. 39, No. 1, 2001, pp. 91-94. doi:10.1159/000052418
S. Lahme, K. H. Bichler, G. Feil and S. Krause, “Comparison of Cytology and Nuclear Matrix Protein 22 for the Detection and Follow-Up of Bladder Cancer,” Urologia Internationalis, Vol. 66, No. 2, 2001, pp. 72-77. doi:10.1159/000056574
S. Eissa, M. Swellam, M. Sadek, S. Mourad, O. Ahmady and A. Khalifa, “Comparative Evaluation of the Nuclear Matrix Protein, Fibronectin, Urinary Bladder Cancer Antigen and Voided Urinary Cytology in the Detection of Bladder Tumors,” Journal of Urology, Vol. 168, No. 2, 2002, pp. 465-469. doi:10.1016/S0022-5347(05)64659-9
S. K. Pattari and P. Dey, “Urine: Beyond Cytology for Detection of Malignancy,” Diagnostic Cytopathology, Vol. 27, No. 3, 2002, pp. 139-142. doi:10.1002/dc.10135
M. Lekili, E. Sener, M. A. Demir, G. Temeltas, T. Muezzinoglu and C. Buyuksu, “Comparison of the Nuclear Matrix Protein 22 with Voided Urine Cytology in the Diagnosis of Transitional Cell Carcinoma of the Bladder,” Urological Research, Vol. 32, No. 2, 2004, pp. 124-128. doi:10.1007/s00240-003-0394-2
V. B. Lokeshwar and M. S. Soloway, “Current Bladder Tumor Tests: Does Their Projected Utility Fulfill Clinical Necessity?” Journal of Urology, Vol. 165, No. 4, 2001, pp. 1067-1077. doi:10.1016/S0022-5347(05)66428-2
K. H. Lee, “Evaluation of the NMP-22 Test and Comparison with Voided Urine Cytology in the Detection of Bladder Cancer,” Yonsei Medical Journal, Vol. 42, No. 1, 2001, pp. 14-18.
A. Di Carlo, D. Terracciano, A. Mariano, A. Oliva, M. D’Armiento and V. Macchia, “Role of Cytokeratins, Nuclear Matrix Proteins, Lewis Antigen and Epidermal Growth Factor Receptor in Human Bladder Tumors,” International Journal of Oncology, Vol. 23, No. 3, 2003, pp. 757-762.
M. Muller, “Telomerase. It’s Clinical Relevance in the Diagnosis of Bladder Cancer,” Oncogene, Vol. 21, No. 4, 2002, pp. 650-655. doi:10.1038/sj.onc.1205071
M. A. Sanchini, R. Gunelli, O. Nanni, S. Bravaccini, C. Fabbri, A. Sermasi, E. Bercovich, A. Ravaioli, D. Amadori and D. Calistri, “Relevance of Urine Telomerase in Diagnosis of Bladder Cancer,” Journal of the American Medical Association, Vol. 294, No. 16, 2005, pp. 2052-2056. doi:10.1001/jama.294.16.2052
Y. Takihana, T. Tsuchida, M. Fukasawa, I. Araki, N. Tanabe and M. Takeda, “Real-Time Quantitative Analysis for Human Telomerase Reverse Transcriptase Mrna And Human Telomerase RNA Component Mrna Expressions as Markers for Clinicopathologic Parameters in Urinary Bladder Cancer,” International Journal of Urology, Vol. 13, No. 4, 2006, pp. 401-408.
S. Bravaccini, M. A. Sanchini, A. M. Granato, R. Gunelli, O. Nanni, D. Amadori, D. Calistri and R. Silvestrini, “Urine Telomerase Activity for the Detection of Bladder Cancer in Females,” Journal of Urology, Vol. 178, No. 1, 2007, pp. 57-61. doi:10.1016/j.juro.2007.03.025
A. Bennett, “Telomerase and Other Novel Approaches to Bladder Cancer Detection,” Clinical and Laboratory Science, Vol. 21, No. 3, 2008, pp. 185-190.
L. Mezzasoma, C. Antognelli, C. Del Buono, F. Stracci, E. Cottini, G. Cochetti, V. N. Talesa and E. Mearini, “Expression and Biological-Clinical Significance of hTR, hTERT and CKS2 in Washing Fluids of Patients with Bladder Cancer,” BMC Urology, Vol. 10, 2010, p. 17. doi:10.1186/1471-2490-10-17
Z. Li, C. Kong, P. Wang, X. Liu and T. Liu, “Telomerase Activity in Urine in Diagnosis and Recurrence Surveillance of Urothelial Carcinoma,” Chinese Medical Journal, Vol. 115, No. 11, 2002, pp. 1650-1652.
S. Eissa, M. Swellam, A. Amin, M. E. Balbaa, G. A. Yacout and T. M. El-Zayat, “The Clinical Relevance of Urine-Based Markers for Diagnosis of Bladder Cancer,” Medical Oncology, Vol. 28, No. 2, 2011, pp. 513-518. doi:10.1007/s12032-010-9422-6
S. Weikert, H. Krause, I. Wolff, F. Christoph, M. Schrader, T. Emrich, K. Miller and M. Muller, “Quantitative Evaluation of Telomerase Subunits in Urine as Biomarkers for Non Invasive Detection of Bladder Cancer,” International Journal of Cancer, Vol. 117, No. 2, 2005, pp. 274-280. doi:10.1002/ijc.21168
I. A. Abd El Gawad, H. S. Moussa, M. I. Nasr, E. H. El Gemae, A. M. Masooud, I. K. Ibrahim and N. M. El Hifnawy, “Comparative Study of NMP-22, Telomerase, And BTA in the Detection of Bladder Cancer,” Journal of the Egyptian National Cancer Institute, Vol. 17, No. 3, 2005, pp. 193-202.
U. Kumar, P. Dey, A. K. Mondal, S. K. Singh and H. Vohra, “DNA Flow Cytometry and Bladder Irrigation Cytology in Detection of Bladder Carcinoma,” Diagnostic Cytopathology, Vol. 24, No. 3, 2001, pp. 153-156. doi:10.1002/1097-0339(200103)24:3 3.0.CO;2-P
M. S. Soloway, J. V. Briggman and G. A. Carpinito, “Use of a New Tumor Marker, Urinary NMP-22, in the Detection of Occult or Rapidly Recurring Transitional Cell Carcinoma of the Urinary Tract Following Surgical Treatment,” Journal of Urology, Vol. 156, No. 2, 1996, pp. 363-367. doi:10.1016/S0022-5347(01)65851-8
R. Srivastava, V. K. Arora, S. Aggarwal, A. Bhatia, N. Singh and V. Agrawal, “Cytokeratin-20 Immunocyto-chemistry in Voided Urine Cytology and Its Comparison With Nuclear Matrix Protein-22 and Urine Cytology in the Detection of Urothelial Carcinoma,” Diagnostic Cytopathology, 6 January 2011, In Press.
V. Poulakis, U. Witzsch, R. De Vries, H. M. Altmannsberger, M. J. Manyak and E. Becht, “A Comparison Of Urinary Nuclear Matrix Protein-22 and Bladder Tumor Antigen Tests with Voided Urinary Cytology in Detecting And Following Bladder Cancer: The Prognostic Value of False-Positive Results,” British Journal of Urology International, Vol. 88, No. 7, 2001, pp. 692-701. doi:10.1046/j.1464-410X.2001.02355.x