p53 and MDM2 in the development and progression of bladder cancer.
OBJECTIVE
Earlier investigations have demonstrated that inactivation of the p53 tumor suppressor gene might play a role in the development and progression of bladder cancer. Complex formation with the MDM2 oncogene product is one mechanism inactivating the p53 protein. Therefore, the MDM2 and the p53 protein were investigated to study potential interactions in bladder cancer.


METHODS
200 archival bladder tissue specimens from 92 patients were studied by immunohistochemistry using monoclonal antibodies DO-1 against p53 and IF2 against MDM2.


RESULTS
No staining was observed for p53 or MDM2 in normal urothelium. Alterations of both genes were rare in dysplasia. p53 accumulation was observed in 27-44% of the tumor stages examined. MDM2 overexpression increased from 18% in carcinoma in situ to 49% in T1 tumors, but was present in only 22% of the advanced tumors. Alterations of both genes were more frequent in high-grade lesions. To investigate the prognostic impact of these alterations 61 patients with superficial bladder tumors were followed for at least 2 years (mean 51 months). Multivariate analysis demonstrated that multifocal disease and p53 accumulation were significantly correlated with tumor progression (p = 0.0099 and 0.0135). MDM2 overexpression alone had no prognostic significance. Patients with alterations of both genes had a very high risk of tumor progression (p = 0.0064).


CONCLUSIONS
These results demonstrate a positive correlation between p53 accumulation and MDM2 overexpression in the progression of bladder cancer which may have prognostic value.
Schmitz-Dräger
B J
BJ
Urologische Klinik, Heinrich-Heine-Universität, Düsseldorf, Deutschland.
Kushima
M
M
Goebell
P
P
Jax
T W
TW
Gerharz
C D
CD
Bültel
H
H
Schulz
W A
WA
Ebert
T
T
Ackermann
R
R
D002278:Carcinoma in Situ / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2