title: Nuclear Protein Phosphatase 1 α (PP1A) Expression is Associated with Poor Prognosis in p53 Expressing Glioblastomas.
abstract: BACKGROUND
  Protein phosphatase 1 α (PP1A) is an enzyme intimately associated with cell cycle, the over expression of which has been demonstrated in glioblastoma (GBM). Further, the nuclear expression of PP1A has been shown to be highly specific to GBM. In addition, PP1A has been shown to be a connecting molecule in the p53 containing GBM sub network. In view of these, we evaluated the prognostic relevance of PP1A.
  
  
  METHODS
  GBM tissues were examined for protein expression of PP1A by immunohistochemistry (IHC). Nuclear expression of PP1A was scored in all tumor tissue samples. Survival analyses were performed by Cox-Regression and Kaplan-Meier survival analysis with Log Rank tests. IDH1, ATRX and p53 IHC and stratification of all GBM cases were performed and subgroup specific evaluation of nuclear PP1A correlation with overall and progression free survival was performed.
  
  
  RESULTS
  PP1A protein expression showed no correlation with prognosis in all cases of GBM or on stratification based on IDH1 or ATRX expression. However on p53 stratification nuclear PP1A expression emerged as strong independent predictor of poor overall survival only in p53 positive GBMs both in univariate and multivariate analysis.
  
  
  CONCLUSIONS
  While PP1A expression uniquely associates with poor prognosis only in p53 expressing GBMs, there is a notable absence of such correlation in p53 negative GBMs; thus skewing the overall relation of this molecule with prognosis in GBM. PP1A emerging as a strong prognostic marker in p53 expressing GBMs, enables us to foresee this molecule as a potential therapeutic target.
authors.affiliation: Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India.
authors.forename: Arun H
authors.initials: AH
authors.lastname: Shastry
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India.
authors.forename: Balaram
authors.initials: B
authors.lastname: Thota
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India.
authors.forename: Mallavarapu R
authors.initials: MR
authors.lastname: Srividya
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India.
authors.forename: Arimappamagan
authors.initials: A
authors.lastname: Arivazhagan
authors.affiliation: Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India. vani.santosh@gmail.com.|Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India. vani.santosh@gmail.com.
authors.forename: Vani
authors.initials: V
authors.lastname: Santosh
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D054645:Protein Phosphatase 1
keywords: Glioblastoma; PPP1CA; Prognosis; Protein phosphatase 1 α; TP53