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Departments of Pathology [C. C-C., M. D., E. C., V. E. R.] and Epidemiology & Biostatistics [Z-F. Z.] and the Urology Service Department of Surgery [G. D.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and Departments of Hematology [S-X. H., W. F. B.] and Molecular Oncology [H-J. X.], M. D. Anderson Cancer Center, Houston, Texas 77030
Altered patterns of p53 and pRB expression have been reported to be frequent events and to have prognostic significance in bladder cancer. To assess the potential adverse consequences of having altered patterns of both p53 and pRB proteins in patients with bladder neoplasms compared with having one or neither abnormality, we have studied a cohort of superficial transitional cell carcinomas of the urinary bladder by immunohistochemical analysis. The present study included 59 well-characterized superficial transitional cell carcinomas (Ta, n = 28; T1, n = 31) for which clinicopathological variables were available. Nuclear overexpression of p53 was identified in 22 cases (37%). A statistically significant association was observed between the p53-positive phenotype and disease progression (P < 0.001), as well as reduced survival (P < 0.001). Undetectable levels of pRB were observed in 11 cases (19%). Patients with a pRB-negative phenotype had a more frequent disease progression (P = 0.014) and decreased overall survival (P = 0.014). We also observed a significant association between altered p53 and undetectable pRB expression patterns (P = 0.001). Nine tumors showed both a p53-positive and a pRB-negative phenotype. There was an even more marked increase in progression (P = 0.0005) and decreased overall survival (P = 0.0004) in patients whose tumors had both alterations after controlling for tumor stage, tumor grade, and suspicion of vascular invasion. These data suggest that alterations of p53 and pRB have a cooperative negative effect on both progression and survival in primary bladder cancer. It may be postulated that aberrant p53 and pRB expression deregulates cell cycle control at the G1 checkpoint and engenders tumor cells with reduced response to programmed cell death. The imbalance produced by an enhanced proliferative activity and a decreased apoptotic rate may determine the aggressive clinical course of the bladder tumors harboring both p53 and pRB alterations.
1 This work was supported in part by NIH Grants CA-47538 and ES-06718 (to C. C-C. and Z-F. Z.) and NIH Grant CA-54672 (to W. F. B.).
2 To whom requests for reprints should be addressed, at Department of Pathology, Division of Molecular Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-7746; Fax: (212) 794-3186.
Received 11/27/96. Accepted 2/14/97.
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