ERG, TMPRSS2 and SLC45A3 Expression in Prostate Cancers with Rearrangements of these Genes.
Niels J Rupp, Sven Perner, Martin Braun, Holger Moch, Falko Fend, Mark A Rubin, Glen Kristiansen. University Hospital Bonn, Germany; University Hospital Zürich, Switzerland; University Hospital Tübingen, Germany; Weill Cornell Medical College, New York, NY
Background: The majority of prostate cancer harbours recurrent gene fusions involving ERG, a member of the ETS gene family, and the 5' untranslated region of the androgen regulated TMPRSS2 gene and less commonly the prostate specific solute carrier SLC45A3 gene. The aim of our study was to quantify the protein expression of ERG, TMPRSS2 and SLC45A3 in a large prostatectomy cohort with known gene rearrangement status of these genes and to assess for diagnostic or prognostic capabilities.
Design: We analysed tumors from 640 cases with known TMPRSS2-ERG and SLC45A3-ERG gene rearrangement status for protein expression of these genes on tissue microarrays using commercially available antibodies and a four class scoring system (negative, weak, moderate and strong). Resultant data was correlated to the respective gene rearrangement status and clinico-pathological parameters including PSA follow up data.
Results: Protein expression analysis for ERG showed no expression in benign prostate glands as compared to an average low expression in the cancerous tissue. In cancer tissue, high ERG protein expression was strongly associated with a positive rearrangement status (r = 0.647; p < 0.0001) but showed no correlation with outcome data. In 23 of 218 cases (11%) ERG protein was expressed without evidence of gene rearrangement and 58 of 253 cases (23%) showed no ERG protein expression despite positive gene rearrangement status.
SLC45A3 exhibited a significantly weaker protein expression in the prostate cancer samples in relation to the benign tissue and revealed a significantly negative association with the rearrangement status in the cancerous tissue. Correlations with outcome data showed a significantly shorter survival time for patients with lower SLC45A3 protein expression.
No significant protein expression difference was found for TMPRSS2 between benign and malignant tissue. Furthermore, no correlation between protein expression and rearrangement status in the malignant glands could be detected.
Conclusions: This study confirms that ERG protein expression is highly restricted to prostate carcinomas that harbor the ERG rearrangement but does not occur in benign glands and might therefore be a relevant diagnostic marker for ERG-rearranged prostate cancer. The negative prognostic value of SLC45A3 protein expression clearly warrants further study.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 103, Monday Afternoon