Objective: At present, there are no predictors of tumour behaviour for grade (G) 2 pTa transitional cell carcinomas (TCC) of the bladder. Here we analyse the prognostic relevance of histopathological grading and the immunohistochemical detection of p53 and p21/WAF1. Methods: 70 patients were newly diagnosed with G2 pTa TCC of the bladder based on transurethral resection specimens. Two pathologists, blinded with respect to the clinical outcome, confirmed the initial grade and subclassified the G2 lesions into G2a and G2b carcinomas based on the degree of nuclear atypia and the number of mitoses. Immunoreactivity for p53 and p21/WAF1 was evaluated semiquantitatively. Results: There were 52 G2a and 18 G2b tumours, mean follow–up was 49.2 months. Of all patients, 31.4% remained tumour–free, 48.6% recurred with the same tumour grade and stage, and 20.0% showed tumour progression. Patients with G2a tumours developed tumour progression in 13% in contrast to 39% with G2b lesions (p = 0.037). Of 21 p53–positive tumours, 33% (7/21) developed progressive disease, whereas 14% (7/49) of p53–negative patients showed tumour progression (p = 0.102). Neither p21/WAF1 expression alone nor the combination of p53 and p21/WAF1 correlated with clinical outcome. Conclusion: The more detailed grading system but not p53 or p21/WAF1 immunohistochemistry was found to be an independent prognostic factor for tumour progression.

Keywords:
Bladder carcinoma, Grading, Immunohistochemistry, p53, p21/WAF1, Pathology, Prognosis
1.
Thorpe AC, Jenkins BJ, Martin JE: Management of superficial G2 (pTa and pT1) bladder cancer. Urology 1990;36:395–397.
2.
Torti FM, Lum BL, Aston D, MacKenzie N, Faysel M, Shortliffe LD, Freiha F: Superficial bladder cancer: The primacy of grade in the development of invasive disease. J Clin Oncol 1987;5:125–130.
3.
Pauwels RPE, Schapers RFM, Smeets AWGB, Debruyne FMJ, Geraedts JPM: Grading in superifical bladder cancer. Morphological criteria. Br J Urol 1988;61:129–134.
4.
Carbin B, Ekman P, Gustafson H, Christensen NJ, Sandstedt B, Silferswärd C: Grading of human urothelial carcinoma based on nuclear atypia and mitotic frequency. I. Histological description. J Urol 1991;145:968–971.
5.
Keegan PE, Lunec J, Neal DE: p53 and p53–regulated genes in bladder cancer. Br J Urol 1998;82:710–720.
6.
Leissner J, Gerber M, Fischer U, Mitze M, Steinbach F, Stöckle M: Predictive value of p53 accumulation in patients with locally advanced bladder cancer. J Urol 1996;155:615A.
7.
Inagaki T, Ebisuno S, Uekado Y, Hirano A, Shinka T, Ohkawa T: PCNA and p53 in urinary bladder cancer: Correlation with histological findings and prognosis. Int J Urol 1997;4:172– 176.
8.
El–Deiry W, Harper JW, O’Connor P, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn KW, Elledge SJ, Kinzler KW, Vogelstein B: WAF1/CIP1 is induced in p53–mediated G1 arrest and apoptosis. Cancer Res 1994;54:1169–1174.
9.
Michieli P, Chedid M, Lin D: Induction of WAF1/CIP1 by a p53–independent pathway. Cancer Res 1994;54:3391–3396.
10.
Garcia JF, Piris MA, Lloret E, Oradre JL, Murillo PG, Martinez JC: p53 expression in CMV–infected cells: Association with the alternative expression of the p53 transactivated genes p21/WAF1 and MDM2. Histopathology 1997;30:120–125.
11.
Mostofi F, Sobin LH, Torloni H: Histological typing of urinary bladder tumours. International Histological Classification of Tumours, No 10. Geneva, WHO, 1973.
12.
Sobin LH, Wittekind C: TNM Classification of Malignant Tumors, ed 5. New York, Wiley–Liss, 1997.
13.
Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457–481.
14.
Abel PD, Hall RR, Williams G: Should pT1 transitional cell cancers of the bladder still be classified as superficial? Br J Urol 1988;62: 235–239.
15.
Heney NM, Ahmed S, Flanagan MJ, Frable W, Corder MP, Hafermann MD: Superficial bladder cancer: Progression and recurrence. J Urol 1983;130:1083–1086.
16.
Anderström C, Johannson S, Nilsson C: The significance of lamina propria invasion on the prognosis of patients with bladder tumors. J Urol 1980;124:23–26.
17.
Holmäng S, Hedelin H, Anderström C, Johannson SL: The relationship among multiple recurrences, progression and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years. J Urol 1995;153:1823–1827.
18.
Carbin B, Ekman P, Gustafson H, Christensen NJ, Silferswärd C, Sandstedt B: Grading of human urothelial carcinoma based on nuclear atypia and mitotic frequency. II. Prognostic importance. J Urol 1991;145:972–976.
19.
Schapers RF, Pauwels RP, Wijnen JT: A simplified grading method of transitional cell carcinoma of the urinary bladder: Reproducibility, clinical significance and comparison with other prognostic parameters. Br J Urol 1994; 73:625–631.
20.
Mostofi FK, Davis CJ, Sesterhenn IA: Histological Typing of Urinary Bladder Tumours, ed 2. Berlin, Springer, 1999.
21.
Lipponen P, Aaltomaa S, Eskelinen M, Ala–Opas M, Kosma VM: Expression of p21(waf1/ cip1) protein in transitional cell bladder tumours and its prognostic value. Eur Urol 1998;34:237–243.
22.
Stein JP, Ginsberg DA, Grossfeld GD, Chatterjee SJ, Esrig D, Dickinson MG: Effect of p21 WAF/CIP1 expression on tumor progression in bladder cancer. J Natl Cancer Inst 1998;90: 1072–1079.
23.
Osen L, Fossa SD, Majak B, Rotterud R, Berner A: Prognostic factors in muscle–invasive bladder cancer treated with radiotherapy: An immunohistochemistry study. Br J Urol 1988; 81:862–869.
24.
Zlotta AR, Noel JC, Fayt I, Drowart A, van Vooren JP, Huygen K, Simon J, Schulman CC: Correlation and prognostic significance of p53, p21 WAF/CIP1 and Ki–67 expression in patients with superficial bladder tumors treated with Bacillus Calmette–Guérin intravesical therapy. J Urol 1999;161:792–798.
25.
Clasen S, Schulz WA, Gerharz CD, Grimm MO, Cristof F, Schmitz–Dräger BJ: Frequent and heterogeneous expression of cyclin–dependent kinase inhibitor WAF1/p21 protein and mRNA in urothelial carcinoma. Br J Cancer 1998;77:515–521.
2001
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