Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell carcinoma of the bladder.
We investigated the prognostic and predictive relevance of p53, MDM2, and bcl-2 protein expression in patients with transitional cell carcinoma (TCC) of the bladder. The expression of p53, MDM2 and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded specimens from 119 patients whose clinicopathologic data confirmed TCC of the bladder. Multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters were examined. Sixty-one, 12, and 17% of cases were considered positive for expression of p53, MDM2 and bcl-2, respectively. p53 expression correlated with stage (p=0.0209), but not MDM2 and bcl-2 with any clinicopathologic parameters. In Cox's regression analysis, staging demonstrated a statistically worse prognosis (hazard ratio 1.636; p=0.0059) while bcl-2 (hazard ratio 0.179; p=0.0474) expression showed favorable prognosis in stage T2-4 invasive TCC of the bladder. Co-expression with p53/MDM2 (hazard ratio 0.367; p=0.0401) and p53/bcl-2 (hazard ratio 3.487; p=0.0111) overexpression were associated with favorable and unfavorable prognosis in stage T2-4 invasive TCC of the bladder, respectively. Our results indicate that staging is the most useful parameter to predict clinical outcome in patients with TCC of the bladder. Determinations of bcl-2 and co-expression p53/MDM2 and p53/bcl-2 may be useful for predicting tumor behavior and prognosis in stage T2-4 invasive type TCC of the bladder.
Uchida
T
T
Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 228-8555, Japan. tuchida@green.ocn.ne.jp
Minei
S
S
Gao
J-P
JP
Wang
C
C
Satoh
T
T
Baba
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2