P21(WAF1 CIP1) AND P53 PROTEIN EXPRESSION IN BREAST-CANCER/

p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kin ase [Cdk]-interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a downstream mediator of p53. In this study, we sough t to clarify the clinical significance of Waf1 and the relationship be tween Waf1 and p53 in breast cancer. For this purpose, the expressions of Waf1 and p53 were evaluated immunohistochemically in a series of 1 04 patients. Waf1 was expressed in 51 (49%) of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two proteins was s een in 76 cases (73%); 47 were Waf1-positive and p53-negative, and 29 were Waf1-negative and p53-positive. A comparison with clinicopatholog ic parameters showed that Waf1 expression correlated with negative lym ph nodes (P<.01), a low histologic grade (P<.0001), and positive estro gen receptor status (P<.01). Recurrence-free survival was lower for pa tients with Waf1-negative tumors than for those with Waf1-positive tum ors (P<.0001). In multivariate analysis, Waf1 expression and low histo logic grade (1 or 2) tumors had an independent prognostic significance for recurrence-free survival. These results suggest that Waf1 is indu ced mainly by a p53-dependent pathway and could be a reliable indicato r of recurrence in breast cancer.