Protein phosphatase magnesium-dependent 1δ (PPM1D) expression as a prognostic marker in adult supratentorial diffuse astrocytic and oligodendroglial tumors

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 a mutation in the PPM1D gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluated the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodendroglial tumors. Methods: To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope in situ hybridization, and fluorescence in situ hybridization were performed in 84 adult supratentorial diffuse gliomas. 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 cases (54.8%) were PPM1Dpositive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (p =.035), but marginally with PPM1D gene amplification (p =.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (p