Pretreatment p53 nuclear overexpression as a prognostic marker in superficial bladder cancer treated with Bacillus Calmette-Guérin (BCG).
BACKGROUND
Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisit the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG.


METHODS
From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei.


RESULTS
Immunostaining was significantly higher for Ta/T1 G3 +/- Cis (p < 0.001), tumoral substage T1b (p = 0.001), grade 3 (p = 0.0001), and Cis (p = 0.002). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p = 0.03; p < 0.0001; p = 0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p = 0.0003) [RR = 0.15; 95%CI, 0.06 to 0.42].


CONCLUSIONS
Pretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG.
Saint
Fabien
F
Department of Pathology, Hôpital Henri Mondor, 94000 Créteil, France. fabiensaint@hotmail.com
Le Frere Belda
Marie-Aude
MA
Quintela
Rodrigo
R
Hoznek
Andras
A
Patard
Jean-Jacques
JJ
Bellot
Jacqueline
J
Popov
Zivko
Z
Zafrani
Elie S
ES
Abbou
Claude C
CC
Chopin
Dominique K
DK
de Medina
Sixtina Gil Diez
SG
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics*; D002467:Cell Nucleus; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics*
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D016159:Tumor Suppressor Protein p53