Wild-type p53 inducible phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can be partly developed without TP53 mutation. In such cases, the p53 pathway may be disrupted by alternative mechanisms, and Wip1 is reported to be one of the key molecules.
Primary invasive ductal carcinoma specimens were obtained from 201 patients. We evaluated Wip1 mRNA expression, Wip1 and p21 protein expression, PPM1D DNA copy number and their relationships with the clinicopathological factors and the prognosis.
Nuclear expression of Wip1 protein was positive in 21 cases (10.4%). PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism-comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. Wip1 protein expression was significantly associated with poor recurrence-free survival (RFS) (p = 0.0274). However, there was no signiﬁcant correlation between Wip1 protein expression and overall survival (OS). There was no significant correlation between p21 expression and prognosis. In terms of the combination analysis of Wip1 and p21 expression, Wip1 positive and p21 negative cases showed the significantly shorter PFS and relatively shorter OS compared to the other groups.
Wip1 protein expression may be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression showed the poorest prognosis and suggests the loss of p53 function.
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All authors have declared no conflicts of interest.