p53 and Bcl-2 Overexpression as Associated Risk Factors in Patients 40 Years Old or Less with Transitional Cell Carcinoma of the Bladder

Abstract

Objectives: Transitional cell carcinoma (TCC) of the bladder in younger patients has historically a favourable prognosis. bcl-2 and p53 genes are implicated in cell cycle regulation with roles on programmed cell death. Presence of nuclear accumulation of p53 and cytoplasmic accumulation of bcl-2 were proposed to confer a growth advantage to tumour cells. In this study, we investigated the roles of p53 and bcl-2 as prognostic factors in TCC of bladder in patients younger than 40 years. Patients and Methods: From 1986 to 1998, 25 patients younger than 40 years were treated for TCC of bladder in our hospital. Of the tumour specimens, 24 were adequate for evaluating p53 and bcl-2 oncoproteins (group I). As a control (group II), we randomly selected 30 patients older than 50 years treated for bladder cancer in this period. Two oncoproteins were detected by immunohistochemical analysis in paired tumour tissue specimens in both groups. Retrospectively obtained clinical follow-up data were available, with a mean follow-up of 44 and 25.5 months in groups I and II, respectively. Relations between tumour recurrences and progression with positivity of bcl-2 and p53 were investigated. Results: Expression of bcl-2 was observed in 13 (54.1%) and 11 (36.7%) and nuclear p53 accumulation in 9 (37.5%) and 17 (56.7%) of groups I and II, respectively. In the presence of p53 expression, tumours showed significantly more progression in group I (55 vs. 6.7%) and group II (41.1 vs. 0%). Recurrence rates were not significantly different in tumours with and without nuclear p53 overexpression in both groups. Also, recurrence and progression rates were not significantly different in tumours with and without cytoplasmic bcl-2 overexpression in both groups. Grade (G) and stage appeared as important prognostic factors in both groups since 60% of GIII tumours showed progression in group I, but none of GI and GII tumours. Similarly, 75% of T3 tumours progressed, while these rates were 25 and 25% for T1-T2 tumours in group I. In group II, 31.2, 25 and 0% of GIII, GII and GI tumours progressed, while 50, 41.6 and 0% of T3, T2 and T1 tumours progressed, respectively. Conclusions: Nuclear p53 expression in TCC appears to be associated with a poorer prognosis in both younger and older patients. Although cytoplasmic bcl-2 overexpression is found in the majority of tumours in the younger group, it is not associated with tumour progression and recurrence. Copyright © 2001 S. Karger AG, Basel.