Subcellular Localization of p27(kip1) in Breast Cancer and Its Prognostic Significance

ABSTRACT

BACKGROUND: p27 is a member of the cyclin-dependent kinase (CDK) inhibitors that arrest the progression of the cell cycle; thus, it acts as a tumor suppressor gene. The loss or decrease of p27 protein is frequently seen and this has an independent prognostic potential for many human cancers. p27 is functionally inactivated through accelerated proteolysis and cytoplasmic sequestration. Cytoplasmic mislocalization of p27 by abnormal phosphorylation in the tumor cells doesn't allow it to bind and inhibit nuclear cyclin/CDK targets. METHODS: We examined the p27 protein expression in 86 cases of invasive ductal carcinoma of the breast via immunohistochemical staining to evaluate the subcellular localization of p27 and its relationship with the clinicopathologic features and the prognostic factors. RESULTS: The nuclear expression of p27 was noted in 48.9% of the tumors, a combined nuclear and cytoplasmic expression was noted in 20.9%, a cytoplasmic expression was noted in 12.8%, and a negative expression was noted in 17.4%. The decreased nuclear expression and/or cytoplasmic mislocalization of p27 were statistically correlated with the nuclear grade (p=0.001), histologic grade (p=0.036), tumor size (p=0.033), lymph node metastasis (p=0.043), ER (p=0.001), and PR (p=0.001) status, while they were not correlated with patient age, stage, HER2, p53, and Ki67. CONCLUSIONS: The breast tumors showing both decreased nuclear expression and cytoplasmic mislocalization of p27 are associated with a deranged cell cycle via functional inactivation and also with poor prognostic factors. It is expected that p27 can be a promising anticancer target molecule for the treatment of breast cancer.