Clinical Breast Cancer. 18(4):e643–e650, AUGUST 2018

DOI: 10.1016/j.clbc.2017.11.008

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PMID: 29275106

Issn Print: 1526-8209

Publication Date: August 2018


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Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer

Yuka Inoue;Nami Yamashita;Hiroyuki Kitao;Kimihiro Tanaka;Hiroshi Saeki;Eiji Oki;Yoshinao Oda;Eriko Tokunaga;Yoshihiko Maehara;

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Abstract

The nuclear expression of wild type p53-induced phosphatase 1 (Wip1) protein was found to be positive in 21 patients (10.4%) out of 201 breast cancer patients in our study. The protein phosphatase magnesium dependent 1 delta DNA copy number was significantly correlated with Wip1 protein expression, which was positively correlated with p21 expression. Tumors with positive Wip1 expression and negative p21 expression showed the poorest prognosis of all tumors examined.Background:Wild type p53-induced 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 sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved.Materials and Methods:Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available. We evaluated Wip1 and p21 protein expression (201 cases), Wip1 mRNA expression (63 cases), PPM1D DNA copy number (71 cases) and TP53 status (36 cases) using available samples among the 201 cases, and analyzed their relationships with clinicopathological factors and prognosis.Results:The nuclear expression of Wip1 protein was positive in 21 cases (10.4%). The 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. The tumors with positive Wip1 and negative p21 expression showed the poorest prognosis among all tumor types.Conclusion:The protein expression of Wip1 might be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression was associated with the poorest prognosis and suggests the loss of p53 function.

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