Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma.
OBJECTIVE
To improve our understanding of the clinical relevance of p53, mdm2, and bcl-2 protein overexpression in renal cell carcinoma, we retrospectively investigated the immunohistochemical expression of p53, murine double minute 2 (mdm2), and bcl-2 and the relationship of this expression to clinicopathologic characteristics. p53 regulates the transcription of downstream effectors such as the oncoprotein mdm2, and bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53.


METHODS
The expression of p53, mdm2, and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 112 patients whose clinicopathologic data confirmed renal cell carcinoma.


RESULTS
The expression of the p53 and bcl-2 protein was recognized in 15 (13.4%) and 52 (42.0%) cases, respectively; the expression of the mdm2 protein, however, was seen in only 2 cases (1.8%). No correlation was noted between these three proteins and any clinicopathologic parameters, except p53 expression and Stage T1-2/T3-4 (P = 0.0208). However, in multivariate analysis, stage (hazard ratio 3.586; P = 0.0002), expression of p53 (hazard ratio 6.090; P = 0.0126) and of mdm2 (hazard ratio 22.016; P = 0.0156), and coexpression of p53/mdm2 (hazard ratio 6.146; P = 0.0005) demonstrated a statistically significant effect on prognosis by proportional hazards regression tests.


CONCLUSIONS
Our results indicate that stage, p53 expression, mdm2 expression, and coexpression of p53/mdm2 are useful to predict the clinical outcome in patients with renal cell carcinoma.
Uchida
Toyoaki
T
Department of Urology, Kitasato University School of Medicine, Sagamihara, Japan.
Gao
Jiang Ping
JP
Wang
Chunxi
C
Jiang
Shi Xu
SX
Muramoto
Masatoshi
M
Satoh
Takefumi
T
Minei
Sadanori
S
Shimura
Satoru
S
Irie
Akira
A
Kameya
Toru
T
Baba
Shiro
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002292:Carcinoma, Renal Cell / Q000737:chemistry*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D009363:Neoplasm Proteins; 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