ELEVATED AND ABSENT PRB EXPRESSION IS ASSOCIATED WITH BLADDER-CANCER PROGRESSION AND HAS COOPERATIVE EFFECTS WITH P53

Rb protein (pRb) expression was evaluated in 185 cases of transitional cell carcinoma of the bladder from patients that underwent radical cy stectomy, Tumors were stratified into three categories based on the pe rcentage of nuclei expressing pRb: (a) 0, 0% of tumor cells showing nu clear reactivity; (b) 1+, 1-50% of tumor cells showing nuclear reactiv ity; and (c) 2+, > 50% of tumor cells showing nuclear reactivity. Case s with undetectable (pRb 0) and high (pRb 2+) pRb reactivity had ident ical rates of recurrence. These cases had significantly higher recurre nce (P = 0.0001) and loser survival rates (P = 0.0002) compared to cas es with moderate (pRb 1+) pRb reactivity. indicating that high levels of pRb expression may reflect a dysfunctional (altered) Rb pathway, Th e tumors were also examined for alterations in p53 expression; patient s 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 alte rations in only one of these proteins had intermediate rates of recurr ence and survival. These results suggest that: (a) bladder cancers,vit h high pRb expression do not show the tumor suppressor effects of the protein; and (bi alteration in both p53 and pRb may act in cooperative or synergistic ways to promote tumor progression.