International Bladder Cancer Network

P53 IMMUNOHISTOCHEMISTRY AND PROGNOSIS IN BLADDER CANCER:
UPDATED RESULTS OF THE ISBC COMBINED ANALYSIS

Schmitz-Dräger Bernd J., Goebell Peter J., Heydthausen Manfred, and The International Study Initiative on Bladder Cancer (ISBC)
Urology, EURO-MED-CLINIC, Fürth, Dept. of Urology, University of Essen, Dept. of Biostatistics,Heinrich-Heine-University, Düsseldorf, Germany



Objectives

Despite numerous trials on its prognostic relevance the impact of p53 accumulation on the prognosis remains unclear. The aim of this multiinstitutional retrospective trial on p53 immunohistochemistry in bladder cancer was to analyse the present data and disclose potential reasons for the conflicting results.


Material and Methods

3207 data sets from 24 different studies were obtained, transformed and statistically analysed using the SPSS software. Herein, the results of the first 1706 patients are given. The study group was composed from 1336 males (78.3%) and 370 females. The mean age was 69.5 years. 1177 patients (69%) had superficial tumors Ta (726), TIS (12) and T1 (439) (42.7, 0.6, and 25.7%, respectively), the median follow-up was 11.1 years. The remaining 523 patients had advanced tumors (>T2) with a median survival time of 1.9 years. Of 1272 patients assessable for survival 299 died of bladder cancer, another 199 from intercurrent disease.


Results

Cumulative survival analysis yielded no differences for sex and age. These factors were also equally distributed among the different centers. In contrast, considerable differences were observed with regard to the distribution of tumor stage, multifocal tumor lesions and tumor progression. Tumor grade and tumor stage were clearly correlated with patient survival. Survival time differed significantly between the different centers indicating patient selection. The number of p53 positive tumor cells was lower (16+24.9%) in superficial as compared to advanced tumors (36+37.6%). Using a breakpoint of 23% positive tumor cells 170 of 684 (25%) assessable patients with  uperficial tumors and 187 of 388 patients (48%) with advanced tumors showed p53 accumulation.


Conclusions

This preliminary analysis of the data demonstrates that differences between the different studies with regard to the prognostic impact of p53 can be explained in most cases, by differing study designs and heterogenous study populations. Cumulative analysis of the data shows that p53 accumulation is highly correlated with tumor stage and grade. This ongoing study should further delineate reasons for the different study results.


 Members and Contributors

 
Bernd J. Schmitz-Dräger, Fürth, Germany
Peter J. Goebell, Essen, Germany
Manfred Heydthausen, Düsseldorf, Germany
Guido Sauter, Basel, Switzerland
Thomas C. Gasser, Basel, Switzerland
Yves Fradet, Quebec, Canada
Helene LaRue, Quebec, Canada
Pertti K. Lipponen, Kuopio, Finland
Tapani JO Liukkonen, Mikkeli, Finland
Pertti Rajala, Mikkeli, Finland
M´Liss Ann Hudson, Washington, USA
Peter A. Humphrey, Washington, USA
Giovanni Casetta, Torino, Italy
Alessandro Tizziani, Torino, Italy
Stefan Wellek, Mannheim, Germany
Michael Stöckle, Homburg, Germany
Staffan Jahnson, Ørebrø, Sweden
B. Risberg, Ørebrø, Sweden
Pierfrancesco Bassi, Padova, Italy
Anna Rosa Del Mistro, Padova, Italy
T.R. Leyshon Griffiths, Newcastle, UK
David E. Neal, Newcastle, UK
Mutsuo Furihata, Kochi, Nankoku, Japan
N.N., Nankoku, Japan
Dominique Chopin, Creteil, France
Zivko Popov, Creteil, France
Alan Pollack, Houston, USA
Gunar K. Zagars, Houston, USA
Paolo Dalla Palma, Trento, Italy
Lucio Luciani, Trento, Italy
Lydia Nakopoulou, Athens, Greece
Robert A. Gardiner, Herson, Australia
Mark A. Underwood, Glasgow, UK
Yoshiyuki Kakehi, Kyoto, Japan
Toyoaki Uchida, Kanagawa, Japan
Jack A. Schalken, Nijmegen, The Netherlands
Alexandre R. Zlotta, Bruxelles, Belgium
H. Barton Grossman, Houston, USA
George N. Thalman, Bern, Switzerland
David J. Thomas, Newcastle, UK
Contact:     Bernd J. Schmitz-Dräger, EuromedClinic, Europa-Allee 1, D-90763 Fürth, Germany
bsd@euromed.de