Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

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, β-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1α (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 PP1α (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

Quantifying garnet-melt trace element partitioning using lattice-strain theory: New crystal-chemical and thermodynamic constraints

Many geochemical models of major igneous differentiation events on the Earth, the Moon, and Mars invoke the presence of garnet or its high-pressure majoritic equivalent as a residual phase, based on its ability to fractionate critical trace element pairs (Lu/Hf, U/Th, heavy REE/light REE). As a result, quantitative descriptions of mid-ocean ridge and hot spot magmatism, and lunar, martian, and terrestrial magma oceans require knowledge of garnet-melt partition coefficients over a wide range of conditions. In this contribution, we present new crystal-chemical and thermodynamic constraints on the partitioning of rare earth elements (REE), Y and Sc between garnet and anhydrous silicate melt as a function of pressure (P), temperature (T), and composition (X). Our approach is based on the interpretation of experimentally determined values of partition coefficients D using lattice-strain theory. In this and a companion paper (Draper and van Westrenen this issue) we derive new predictive equations for the ideal ionic radius of the dodecahedral garnet X-site,