Amplification of the mdm-2 gene and overexpression of the mdm-2 protei
n might inactivate p53 function, and may have prognostic relevance. Th
e present paper investigated the immunohistochemical overexpression of
the mdm-2 and p53 proteins in 25 biopsy specimens of transitional cel
l bladder carcinomas (10 pT1 and 15 pT2 or higher stages). Five cases
(20%) showed strong mdm-2 protein immunoreactivity in more than 5% of
the tumor cells; 14 cases (56%) showed p53 immunoreactivity in more th
an 20% of the cells, and were considered as overexpressing p53 protein
. Four of the five cases with strong mdm-2 immunoreactivity did not sh
ow p53 overexpression, and 13 of the 14 cases with p53 overexpression
did not show mdm-2 immunoreactivity. Our data are consistent with the
hypothesis that p53 overaccumulation (and hence possible p53 gene muta
tion) or mdm-2 overexpression (and hence possible mdm-2 gene amplifica
tion) may mirror two different and possibly complementary gene alterat
ions, which might finally interfere with the control of cell prolifera
tion and apoptosis. In this perspective, evaluation of the combined md
m-2/p53 protein phenotype in human bladder carcinomas could have progn
ostic relevance and give us better prognostic information than evaluat
ion of the p53 protein alone.