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doi: https://doi.org/10.4132/jptm.2017.10.21    [Epub ahead of print]
Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodenroglial Tumors
Hui Jeong Jeong1, Chang Gok Woo2, Bora Lee3, Shin Kwang Khang1, Soo Jeong Nam1, Jene Choi1
1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Pathology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
3Department of Biostatistics, Clinical Trial Center, Soonchunhyang Medical Center, Bucheon, Korea
Corresponding Author: Jene Choi ,Tel: +82 2-3010-4555, Fax: +82 2-472-7898, Email: jenec@amc.seoul.kr
Received: August 30, 2017;  Revised: October 16, 2017  Accepted: October 17, 2017.  Published online: October 18, 2017.
ABSTRACT
Background: Protein phosphatase magnesium-dependent 1δ (PPM1D) is a p53-induced serine/threonine phosphatase, which is overexpressed in various human cancers. A recent study reported that the mutation in the PPM1D gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluate the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodenroglial tumors. Methods: To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope in situ hybridization, and fluorescence in situ hybridization in 84 adult supratentorial diffuse gliomas were performed, respectively. We further analyzed clinical characteristics and overall survival (OS) according to PPM1D protein expression, and examined its correlation with other glioma biomarkers such as isocitrate dehydrogenase (IDH) mutation, and p53 expression. Results: Forty-six (54.8%) cases were PPM1D-positive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (P=0.035), but marginally with PPM1D gene amplification (P=0.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (P<0.001). Multivariate analysis demonstrated that PPM1D expression (hazard ratio [HR] 2.58, P=0.032), age over 60 years (HR 2.55, P=0.018), and IDH1 mutation (HR 0.18, P=0.002) were significantly independent prognostic factors; p53 expression had no prognostic significance (P=0.986). The patients with tumor expressing PPM1D showed a shorter OS (P=0.003). Moreover, patients with tumor harboring wild-type IDH1 and PPM1D expression had the worst OS (P<0.001).
Conclusions:
Our data suggest that a subset of gliomas express PPM1D; PPM1D expression is a significant marker of poor prognosis in adult supratentorial diffuse astrocytic and oligodenroglial tumors.
Key Words: PPM1D, IDH1, mutation, diffuse astrocytic and oligodenroglial tumors, supratentorial gliomas, molecular marker
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