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WAF1/CIP1 protein expression in human breast tumors

by S. G. Diab, Y. Y. Yu, S. G. Hilsenbeck, D. C. Allred, R. M. Elledge
Breast Cancer Research and Treatment ()

Abstract

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. CONCLUSION: 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.

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