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Nuclear Protein Phosphatase 1 α (PP1A) Expression is Associated with Poor Prognosis in p53 Expressing Glioblastomas

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Pathology & Oncology Research

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.

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Acknowledgments

We acknowledge Prof. M.R.S Rao, Jawaharlal Nehru Centre for Advanced Scientific Research for his support and guidance. Project investigators and project assistants, involved NIMITLI-CSIR (Neuro-Oncology) project are acknowledged. Arun H Shastry is supported by Indian Council of Medical Research, Government of India, under the MD-PhD/TSS-2, medical scientist training program.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India

    Arun H. Shastry & Vani Santosh

  2. Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India

    Balaram Thota, Mallavarapu R. Srividya & Vani Santosh

  3. Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India

    Arimappamagan Arivazhagan

Authors
  1. Arun H. Shastry
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  2. Balaram Thota
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  3. Mallavarapu R. Srividya
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  5. Vani Santosh
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Correspondence to Vani Santosh.

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Shastry, A.H., Thota, B., Srividya, M.R. et al. Nuclear Protein Phosphatase 1 α (PP1A) Expression is Associated with Poor Prognosis in p53 Expressing Glioblastomas. Pathol. Oncol. Res. 22, 287–292 (2016). https://doi.org/10.1007/s12253-015-9928-5

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