Molecular Diagnostics

British Journal of Cancer (2007) 96, 82–88. doi:10.1038/sj.bjc.6603490 www.bjcancer.com
Published online 5 December 2006

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

I Prowatke1, F Devens1, A Benner2, E F Gröne3, D Mertens1, H-J Gröne3, P Lichter1 and S Joos1

  1. 1Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
  2. 2Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany
  3. 3Division of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany

Correspondence: S Joos, Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg D-69120, Germany. E-mail: s.joos@dkfz.de

Revised 20 September 2006; Accepted 25 October 2006; Published online 5 December 2006.

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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 PP1alpha (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 PP1alpha (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.

Keywords:

prostate cancer, tissue microarray, MYC, beta-adrenergic receptor kinase (BARK1, GRK2) protein phosphatase (PP1alpha, PP2A)