Expression of cell cycle-related proteins p27kip1, p21waf1 and p53 in node-negative invasive ductal carcinoma of the breast

Abstract

669 Background: p27kip1 and p21waf1 proteins are universal inhibitors of cyclin-dependent kinases primarily inducing cell cycle arrest in the G1-S checkpoint, function shared with p53 tumor suppressor protein. We evaluated the expression of p27kip1, p21waf1 and p53 retrospectively in a series of node-negative breast carcinomas (NNBCs), since data regarding their prognostic significance in this tumor are contradictory. Methods: Formalin-fixed, paraffin-embedded tissue from 168 NNBCs was studied by immunohistochemistry, using monoclonal antibodies to p27kip1, p21waf1 and p53. The results were correlated with clinicopathological parameters and outcome. Results: Low p27kip1expression (in <50% of tumor nuclei) and p21waf1 expression (in 10% of tumor nuclei) was detected in 26% of NNBCs. p27kip1 loss was associated with high tumor grade (p<0.0001), age <50 years (p=0.01), and negative ER (p<0.0001) and PR (p=0.007) status. p53 overexpression was associated with negative ER (p<0.0001) and PR (p=0.002) status. No correlation was detected between p21waf1 and the examined parameters. Even though on univariate analysis p21waf1 was associated with disease-free survival (p=0.04), on multivariate analysis the examined proteins were not associated with disease-free or overall survival. Conclusions: Although, p27kip1 loss and p53 overexpression are correlated with high grade and negative steroid receptor status, the expression of these proteins does not affect prognosis of NNBC. p21waf1 expression is not correlated with the standard clinicopathological parameters or outcome in NNBC. No significant financial relationships to disclose.