Significance of Wip1 overexpression in breast cancer: Strong association with hormone receptor expression and nodal metastasis

Background and aim: Wild-type p53-induced phosphatase (Wip1), a serine/threonine phosphatase encoded by Ppm1d, is a protein, induced by p53 in response to DNA damage. Recently, correlation between Ppm1d amplification and erbB2 expression has been reported in breast cancers. However, in vitro experiments provide evidences suggesting a relationship between Wip1 and hormone receptor (HR) activity. The aim of the current study was to clarify the relationship between Wip1 overexpression and the expression of HR and erbB2, and to investigate the prognostic significance of Wip1 in breast cancer. Methods: Using tissue microarrays that contained 743 cases of primary invasive breast cancers, we analyzed Ppm1d copy number and examined the expression of Wip1, HRs, p53 and erbB2 by immunohistochemistry. Results:Ppm1d was amplified in 4.7% of breast cancer tumors, while Wip1 was overexpressed in 20.8%. Wip1 overexpression was associated with low nuclear grade (P= 0.032), higher expression of progesterone receptor (P= 0.001), and increased nodal metastasis (P= 0.013). No statistically significant correlations were identified among other clinicopathologic parameters. Conclusions: The close correlation between Wip1 overexpression, progesterone receptor expression and nodal metastasis suggest that Wip1 expression is closely associated with HR activity and might heighten the malignant properties of breast cancers through hormone-mediated tumor growth and progression.