WAF1 CIP1 PROTEIN EXPRESSION IN HUMAN BREAST-TUMORS/

WAF1/CIP1 a cyclin-dependent kinase inhibitor which is directly induce d by p53 and negatively controls cell Proliferation. To test the hypot hesis that increased levels of WAF1 would be associated with a lower S -phase fraction and better prognosis, WAF1 protein was assessed by imm unohistochemistry (IHC) in 115 node-negative human breast tumors, and results were correlated with established prognostic factors and clinic al 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 cytopl asm, or in non-malignant epithelium. Contrary to expectations, the acc umulation of p53 protein, a surrogate marker of p53 inactivation, was weakly but positively associated with WAF1 expression (p = 0.05). Surp risingly, there was no significant correlation with S-phase fraction, ER or PgR status, tumor size, age, ploidy, nuclear grade, or survival. Conclusion: WAF1 expression is found in the nuclei of a small fractio n of cells in human breast tumors. WAF1 status is not significantly as sociated with cell proliferation, other established prognostic factors , or clinical outcome.