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
- 1Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
- 2Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany
- 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.
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,
-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1
(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
(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,
-adrenergic receptor kinase (BARK1, GRK2) protein phosphatase (PP1
, PP2A)
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