Nuclear Protein Phosphatase 1 alpha (PP1A) Expression is Associated with Poor Prognosis in p53 Expressing Glioblastomas
PATHOLOGY & ONCOLOGY RESEARCH
Authors: Shastry, Arun H.; Thota, Balaram; Srividya, Mallavarapu R.; Arivazhagan, Arimappamagan; Santosh, Vani
Abstract
Background Protein phosphatase 1 alpha (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.
Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays
BRITISH JOURNAL OF CANCER
Authors: Prowatke, I.; Devens, F.; Benner, A.; Groene, E. F.; Mertens, D.; Groene, H-J; Lichter, P.; Joos, S.
Abstract
To identify candidate genes relevant for prostate tumour prognosis and progression, we performed an exhaustive gene search in seven previously described genomic-profiling studies of 161 prostate tumours, and four expression profiling studies of 61 tumours. From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, beta-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1 alpha (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1. These candidates were analysed by immunohistochemistry (IHC) on a tissue microarray containing 651 cores of primary prostate cancer samples and benign prostatic hyperplasias (BPH) from 175 patients. In univariate analysis, expression of PP1 alpha (P = 0.001) was found to strongly correlate with Gleason score. MYC immunostaining negatively correlated with both pT-stage and Gleason score (P < 0.001 each) in univariate as well as in multivariate analysis. Furthermore, a subgroup of patients with high Gleason scores was characterised by a complete loss of BARK1 protein (P = 0.023). In conclusion, our study revealed novel molecular markers of potential diagnostic and therapeutic relevance for prostate carcinoma.