Prognostic Value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 Immunoreactivity in pT1 G3 Urothelial Bladder Carcinomas

Abstract

pT1 G3 bladder carcinomas are heterogeneous with respect to tumor recurrence and progression. Whereas some urologists treat these carcinomas by repeated transurethral resections often followed by intravesical chemotherapy or BCG instillation, others recommend cystectomy after tumor recurrence or early cystectomy after the initial diagnosis. Our goal was to determine the prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak, and Ki-67 immunoreactivity in these tumors. There were 30 patients with a new histopathological diagnosis of pT1 G3 urothelial carcinoma based on a transurethral resection specimen. Representative sections of these specimens were examined for the above markers. All patients were followed up regularly and were classified as being tumor free or having tumor recurrence or progression. The mean follow-up period was 43 months (range: 8–102 months). Twenty-five patients underwent radical cystectomy and 7 of these (28%) suffered from tumor progression and died of bladder cancer. In 5 patients, surgery was limited to a transurethral resection and 4 of these patients developed superficial tumor recurrence. There was a significant difference in tumor-free survival between patients with p53-immunoreactive (mean: 30 months) and p53-negative tumors (mean: 82 months; p = 0.0341). Bcl-2 positivity was also associated with decreased tumor-free survival (p = 0.043). The other markers had no significant prognostic impact. We conclude that p53 and Bcl-2 immunoreactivity labels the most aggressive pT1 G3 bladder carcinomas.

Analysis of HER-2/neu amplification in endometrial carcinoma by chromogenic in situ hybridization. Correlation with fluorescence in situ hybridization, HER-2/neu, p53 and Ki-67 protein expression, and outcome

“…Alteration of the gene (mutation or/and deletion) or protein accumulation occurs in over 50% of the cases. 26 In the present series, overexpression of p53 was seen in 61% of the tumours. In previous series of endometrial carcinoma, the reported rate is quite variable (15-77%), which may reflect the lack of consensus of the scoring methods among the studies.…”

“…Recent data on p53 and Ki-67, which are involved in these processes, have merged as valuable prognostic tools. 26 p53 tumour suppressor gene (17p13) encodes a nuclear phosphoprotein that controls the progression of the cell cycle, as well as apoptosis. Alteration either by mutation or/and deletion, leading to intranuclear protein accumulation in the vast majority of the cases, has been detected in over 50% of tumours.…”

“…Contribution to neoplastic progression and more aggressive biologic behaviour has been suggested. 17,19,[24][25][26][27][28] Ki-67 protein is present in the nucleus of cells that are actively undergoing proliferation (not in G0 or early G1). 29 In several neoplasias, the levels of protein expression correlate well with other proliferation markers (eg mitotic count, S-phase, PCNA, cyclin A and B1), tumour growth, 17 and occasionally with prognosis.…”

p53 immunodetection of liquid-based processed urinary samples helps to identify bladder tumours with a higher risk of progression

“…The relevance of p53 in muscle-invasive, pT1 G3 bladder tumours is well documented, but the prognostic impact of p53 alterations in superficial, low-grade tumours remains uncertain (Friedrich et al, 2001;Wolf et al, 2001). Although some groups have shown that p53 is a significant predictor of bladder tumour progression (Schmitz-Dräger et al, 2000), others have concluded that it provides no prognostic information (Gontero et al, 2000;Friedrich et al, 2001).…”

“…For some authors, p53 overexpression in the urine could aid in predicting prognosis and in identifying cases that are likely to progress from superficial to invasive disease (Wolf et al, 2001).…”