WAF1/CIP1 protein expression in human breast tumors.
WAF1/CIP1 is a cyclin-dependent kinase inhibitor which is directly induced by p53 and negatively controls cell proliferation. To test the hypothesis that increased levels of WAF1 would be associated with a lower S-phase fraction and better prognosis, WAF1 protein was assessed by immunohistochemistry (IHC) in 115 node-negative human breast tumors, and results were correlated with established prognostic factors and clinical outcome. Nuclear staining was observed in malignant cells in 43% of tumors. In most (90%) of the positive tumors, the proportion of cells staining for WAF1 was low (< 10%). WAF1 was not detected in the cytoplasm, or in non-malignant epithelium. Contrary to expectations, the accumulation of p53 protein, a surrogate marker of p53 inactivation, was weakly but positively associated with WAF1 expression (p = 0.05). Surprisingly, there was no significant correlation with S-phase fraction, ER or PgR status, tumor size, age, ploidy, nuclear grade, or survival. WAF1 expression is found in the nuclei of a small fraction of cells in human breast tumors. WAF1 status is not significantly associated with cell proliferation, other established prognostic factors, or clinical outcome.