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Elevated and Absent pRb Expression Is Associated with Bladder Cancer Progression and Has Cooperative Effects with p53¹

Departments of Pathology [R. J. C., M. D. D., S. J. C., J. P. S., S-R. S., C. R. T.], Preventive Medicine [Q-C. T., S. G.], and Urology [D. G. S.], University of Southern California School of Medicine/Norris Comprehensive Cancer Center, Los Angeles, California 90033, and the Departments of Hematology [S. X. H., W. F. B.] and Molecular Oncology [H. J. X.], M. D. Anderson Cancer Center, The Woodlands, Texas 77381

Rb protein (pRb) expression was evaluated in 185 cases of transitional cell carcinoma of the bladder from patients that underwent radical cystectomy. Tumors were stratified into three categories based on the percentage of nuclei expressing pRb: (a) 0, 0% of tumor cells showing nuclear reactivity; (b) 1+, 1–50% of tumor cells showing nuclear reactivity; and (c) 2+, >50% of tumor cells showing nuclear reactivity. Cases with undetectable (pRb 0) and high (pRb 2+) pRb reactivity had identical rates of recurrence. These cases had significantly higher recurrence (P = 0.0001) and lower survival rates (P = 0.0002) compared to cases with moderate (pRb 1+) pRb reactivity, indicating that high levels of pRb expression may reflect a dysfunctional (altered) Rb pathway. The tumors were also examined for alterations in p53 expression; patients with tumors altered in both p53 and pRb had significantly increased rates of recurrence (P < 0.0001) and survival (P < 0.0001) compared to patients with no alterations in either p53 or pRb; patients with alterations in only one of these proteins had intermediate rates of recurrence and survival. These results suggest that: (a) bladder cancers with high pRb expression do not show the tumor suppressor effects of the protein; and (b) alteration in both p53 and pRb may act in cooperative or synergistic ways to promote tumor progression.

¹ Supported by National Cancer Institute Grants CA 70903 (to R. J. C.), CA 71921 (to R. J. C.), and CA 54672 (to W. F. B.).

² To whom requests for reprints should be addressed, at University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033. Phone: (213) 764-3270.

³ M. D. D. and S. J. C. contributed equally to this study.

Received 11/25/97. Accepted 1/28/98.

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