p53 mutations in bladder tumors inactivate the transactivation of the p21 and Bax genes, and have a predictive value for the clinical outcome after bacillus Calmette-Guerin therapy
C. Pfister et al., p53 mutations in bladder tumors inactivate the transactivation of the p21 and Bax genes, and have a predictive value for the clinical outcome after bacillus Calmette-Guerin therapy, J UROL, 162(1), 1999, pp. 69-73
Purpose: We analyze the relationship among p53 mutations, p21 and Bax activ
ation as well as their clinical implication in clinical response to intrave
sical bacillus Calmette-Guerin (BCG) therapy in high grade bladder tumors.
Materials and Methods: We analyzed a prospective series of 60 superficial b
ladder tumors using functional assays in yeast which test the transcription
al competence of p53 and can be used to identify p21 and Pax status. BCG in
stillations were given after initial tumor resection to 26 patients with a
high risk of bladder invasive disease (pT1G3 tumors in 24 and carcinoma in
situ in 2).
Results: No p53 alteration was detected in cases of pTa tumors. In contrast
, p53 mutations were detected in 16 of 24 patients (66%) with pT1 G3 tumors
and in 2 with primary carcinoma in situ. These 18 mutant samples scored al
so mutant for transactivation of p21 and Bax reporter strain. In 26 bladder
tumors treated with BCG instillations there was a statistical difference (
p = 0.0075) in the response to BCG therapy between 18 tumors with and 8 wit
hout alterations using functional assays in yeast.
Conclusions: The p53 mutations, using functional assay in yeast, inactivate
the transcription of p21 and Bax genes, and based on these preliminary res
ults could have a useful predictive value for BCG therapy response in bladd
er cancer.