A review of selected diagnostic and prognostic markers in patients with bladder cancer
Article published in Urologia Polska 2007/60/2.

authors

Wojciech Michalski, Tomasz Demkow: Klinika Nowotworów Układu Moczowego, Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie w Warszawie

keywords

urinary bladder, urinary bladder cancer, diagnostic markers, prognostic markers

summary

Introduction. The gold standard in diagnosing the urinary bladder cancer remains cystoscopy. Due to its being invasive and expensive, other markers are being investigated as diagnostic and prognostic factors. In pursuit of "the ideal marker", the following features are taken into account: sensitivity, specificity, costs, reproducibility, and usefulness in tumours of different clinical stages. The newest studies focus on understanding the biology of the cancer and using molecular techniques.

The aim of the study. The aim of this paper was to present an overview of the literature concerning chosen markers in terms of their sensitivity and specificity. We describe markers used in diagnosing both primary and recurrent tumours as well as prognostic markers implicating the overall and disease-free survival rates. The following are described: voided urine cytology, haematuria tests, BTA stat and BTA TRAK tests, NMP 22, surviving, cytokeratins, HA-HAase test, telomerase, EGFR receptor, MIB-1 HER-2, TP53 gene, mdm-2, bcl 2 and others.

Methods. The cited data were obtained from both original and review articles published in the latest issues of urological periodicals as well as from Medline database.

Results. The described markers are of different sensitivity and specificity. Therefore, their clinical usefulness in diagnosing relapses and prognosing the course of the bladder cancer is different. Their value is often different for different clinical stages and pathological grades. Therefore, further prospective studies are necessary.

references

Habuchi T, Marberger M, Droller MJ et al: Prognostic markers for bladder cancer: International Consensus Panel on bladder tumor markers. Urology 2005, 66 (Suppl 6A), 64-74.
Lokeshvar VB, Habuchi T, Grossman HB et al: Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers. Urology 2005, 66 (Suppl 6A), 35-63.
Wiener HG, Mian C, Haitel A et al: Can urine bound diagnostic tests replace cystoscopy in the management of bladder cancer? J Urol 1998, 159, 1876-1880.
Oosterlinck W, van der Meijden A, Sylvester R et al: Guidelines on Ta T1 (non-muscle invasive) Bladder Cancer. EUA Guidelines 2006, 5-6.
Simon MA, Lokeshwar VB, Soloway MS: Current bladder cancer tests: unnecessary or beneficial? Critical Reviews in Oncology/Hematology 2003, 47, 91-197.
Collier L, Oxford J: Papowawirusy, w Collier L, Oxford J: Wirusologia. Podręcznik dla studentów medycyny, stomatologii i mikrobiologii, Warszawa, PZWL, 1996, str 328-330.
Bubendorf L, Mihatsch MJ: Urinary cytology after renal transplantation. Ther Umsch 2006, 63 (9), 609-614.
Glatz K, Willi N, Barascud A et al: An international telecytologic quiz on urinary cytology reveals educational deficits and absence of a commonly used classification system. Am J Clin Pathol 2006, 126 (2), 294-301.
Khan MA, Shaw G, Paris AM: Is microscopic haematuria a urological emergency? BJU Int 2002, 90 (3), 355-357.
Suzuki Y, Sasagawa I, Abe Y et al: Indication of cystoscopy in patients with asymptomatic microscopic haematuria. Scand J Urol Nephrol 2000, 34 (1), 51-54.
Wu JM, Williams KS, Hundley AF et al: Microscopic haematuria as a predictive factor for detecting bladder cancer at cystoscopy in women with irritative voiding symptoms. Am J Obstet Gynecol 2006, 194 (5), 1423-1426.
Khandra MH, Piskarel RS, Charlton M et al: A prospective analysis of 1930 patients with haematuria to evaluate current diagnostic practice. J Urol 2000, 163 (2), 524-527.
Lokeshwar VB, Soloway MS: Current bladder tumor tests: does their projected utility fulfill clinical necessity? The Journal of Urology 2001, 165, 1067-1077.
Boman H, Hedelin H, Holmang S: Four bladder tumor markers have a disappointingly low sensitivity for small size and low grade recurrence. J Urology 2002, 167 (1), 80-83.
Moussa O, Abol-Enein H, Bissada NK et al: Evaluation of surviving reverse transcriptase - polymerase chain reaction for noninvasive detection of bladder cancer. J Urol 2006, 175 (6), 2312-2316.
Yin W, Chen N, Zhang Y et al: Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder. Mod Pathol 2006, 19 (11), 1487-1497.
Attallah AM, Sakr HA, Ismail H et al: Rapid diagnosis and follow-up of bladder cancer patients using urinary high molecular weight cytokeratins. World J Urol 2006, 24 (3), 345-352.
Melissourgos ND, Kastrinakis NG, Skolarikos A et al: Cytokeratin-20 immunocytology in voided urine exhibits greater sensitivity and reliability than standard cytology in the diagnosis of transitional cell carcinoma of the bladder. Urology 2005, 66 (3), 536-541.
Andreadis C, Touloupidis S, Galaktidon G et al: Serum CYFRA 21-1 in patients with invasive bladder cancer and its relevance as a tumor marker during chemotherapy. J Urol 2005, 174 (5), 1771-1775, discussion 1775-1776.
Eissa S, Kassim SK, Labib RA et al: Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs. Cancer 2005, 103 (7), 1356-1362.
Lokeshwar VB, Schroeder GL, Selzer M et al: Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid - hyaluronidase and BTA stat tests. Cancer 2002, 95 (1), 61-72.
Khalbuss W, Goodison S: Immunohitochemical detection of hTERT in urothelial lesions: a potential adjunct to urine cytology. Cytojournal 2006, 10, 3, 18.
Kraemer K, Schmidt U, Fuessel S et al: Microarray analyses in bladder cancer cells: inhibition of hTERT expression down-regulates EGFR. Int J Cancer 2006, 119 (6): 1276-1284.
Memon AA, Sorensen BS, Melgaard P et al: The relation between survival and expression of HER-1 and HER-2 depends on the expression of HER-3 and HER-4: a study in bladder cancer patients. Br J Cancer 2006, 94 (11), 1703-1709.
Moreno Sierra J: Maestro de las Casas ML, Redondo Gonzales E et al: Epidermal growth factor receptor (EGFR) in the prognosis of bladder carcinoma. Experience of 5 years. Arch Esp Urol 2000, 53940, 323-331.
Popov Z, Gil-Diez-De-Medina S, Ravery V et al: Prognostic value of EGF receptor and tumour cell proliferation in bladder cancer: therapeutic implications. Urol Oncol 2004, 22 (2), 93-101.
Gardmark T, Wester K, De la Torre M et al: Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases. BJU Int 2005, 95 (7), 982-986.
Kruger S, Weitsch G, Buttner H et al: HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int J Cancer 2002, 102 (5), 514-518.
Chakravarti A, Winter K, Wu CL et al: Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 2005, 62 (2), 309-317.
Gandour-Edwards R, Lara PN Jr, Folkins AK et al: Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer 2002, 95 (5), 1009-1015.
Kiyoshima K, Oda Y, Kinukawa N et al: Overexpression of laminin-5 gamma2 chain and its prognostic significance in urothelial carcinoma of urinary bladder: association with expression of cyclooxygenase 2, epidermal growth factor receptor [corrected] and human epidermal growth factor receptor [corrected] 2. Hum Pathol 2005, 36 (5), 522-530.
Wulfing C, von Struensee D, Bierer S et al: Expression of Her2/neu in locally advanced bladder cancer: implication for a molecular targeted therapy. Aktuelle Urol 2005, 36 (5), 423-429.
Eltze E, Wulfing C, von Struensee D, Piechota H et al: Cox-2 and Her2/neu co-expression in invasive bladder cancer. Int J Oncol 2005, 26 (6), 1525-1531.
Jones JS: DNA-based molecular cytology for bladder cancer surveillance. Urology 2006, 67 (3), 35-45.
Tsai YS, Tsai TS, Chow NH et al: Prognostic values of p53 and HER-2/neu coexpression in invasive bladder cancer in Taiwan. Urol Int 2003, 71 (3), 262-70.
Musquera Felip M, Palou Redorta J, Moscatiello P et al: Determination of P53 in infiltrative primary bladder tumors as a prognostic factor for understaging. Arch Esp Urol 2006, 59 (2), 125-131.
Maluf F, Cordon-Cardo C, Verbel D et al: Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment. Ann Oncol, 2006, 17 (11), 1677-1686.
Lopez-Knowles E, Hernandez S, Kogevinas M et al: The p53 pathway and outcome among patients with T1 G3 bladder tumors. Clin Cancer Res 2006, 12 (20 Pt 1), 6029-6036.
Liou LS: Urothelial cancer biomarkers for detection and surveillance. Urology 2006, 67 (3), 25-32.

correspondence