The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder.
BACKGROUND
There is controversy regarding the value of biologic markers as prognostic indicators independent of clinicopathologic parameters in transitional cell carcinoma (TCC) of the bladder. The authors examined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB-1 in TCC of the bladder.


METHODS
Fresh frozen samples from 114 TCCs of the bladder and 13 normal bladders were studied by immunohistochemistry, using monoclonal antibodies MIB-1 for proliferation and PAb 1801 for p53 nuclear overexpression. Scores were determined in each case by counting at least 500 nuclei per slide in 3-5 selected regions. Patients were stratified for both markers into two groups for time-event analysis, according to the median number of nuclei stained. Patients with nuclear staining below the median value of the score were considered negative in the statistical analysis. Quantitative immunostaining was analyzed in relation to the time to recurrence, progression, and cancer death, and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression).


RESULTS
Median nuclear overexpression of p53 was 22% and that of MIB-1 28%. There was a strong association between proliferation and p53 nuclear overexpression (P < 0.0001). Progression free and disease specific survival rate estimates (log rank test) were significantly lower in patients with p53 or MIB-1 scores above 22% and 28%, respectively. Multivariate analysis indicated that stage as well as p53 and MIB-1 immunostaining provided independent prognostic information.


CONCLUSIONS
Quantitative immunohistochemical evaluation of nuclear p53 and MIB-1 immunostaining inexpensively provides prognostic indicators in cases of TCC of the bladder.
Popov
Z
Z
Urologic Clinic, Clinical Center, St. Cyril and Methodius University, Skopje, Macedonia.
Hoznek
A
A
Colombel
M
M
Bastuji-Garin
S
S
Lefrere-Belda
M A
MA
Bellot
J
J
Abboh
C C
CC
Mazerolles
C
C
Chopin
D K
DK
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53