p21(Waf1/Cipl) and p53 Protein Expression in Breast Cancer

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p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kinase [Cdk]–interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a downstream mediator of p53. In this study, we sought to clarify the clinical significance of Wafl and the relationship between Wafl and p53 in breast cancer. For this purpose, the expressions of Wafl and p53 were evaluated immunohistochemically in a series of 104 patients. Wafl was expressed in 51 (49%) of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two proteins was seen in 76 cases (73%); 47 were Wafl-positive and p53-negative, and 29 were Waflnegative and p53-positive. A comparison with clinicopathologic parameters showed that Wafl expression correlated with negative lymph nodes (P<.01), a low histologic grade (P<.0001), and positive estrogen receptor status (P<.01). Recurrence-free survival was lower for patients with Wafl-negative tumors than for those with Waflpositive tumors (P<.0001). In multivariate analysis, Wafl expression and low histologic grade (1 or 2) rumors had an independent prognostic significance for recurrence-free survival. These results suggest that Wafl is induced mainly by a p53-dependent pathway and could be a reliable indicator of recurrence in breast cancer.

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