Loss of SLC45A3 protein (prostein) expression in prostate cancer is associated with SLC45A3‐ERG gene rearrangement and an unfavorable clinical course1. Issue 4 (30th August 2012)

• Record Type: Journal Article
• Authors: Perner, Sven; Rupp, Niels J.; Braun, Martin; Rubin, Mark A.; Moch, Holger; Dietel, Manfred; Wernert, Nicolas; Jung, Klaus; Stephan, Carsten; Kristiansen, Glen
• Is Part Of: International journal of cancer. Volume 132:Issue 4(2013:Feb. 15)
• Page Start: 807
• Page End: 812
• Publication Date: 2012-08-30
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.27733
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The majority of prostate cancer harbors recurrent gene fusions involving ETS transcription factors, most commonly <italic>ERG</italic>. The second most common 5′ fusion partner after <italic>TMPRSS2</italic> is <italic>SLC45A3.</italic> The aim of our study was to quantify the protein expression of ERG, TMPRSS2 and SLC45A3 in prostate cancer to assess for diagnostic or prognostic utility. Six hundred and forty consecutive prostate cancer cases in tissue microarray format were immunohistochemically analyzed for ERG, TMPRSS2 and <italic>SLC45A3</italic> protein. Resultant protein expression data was correlated to the respective gene rearrangement status and clinico‐pathological parameters including PSA follow up times. ERG showed no expression in benign prostate glands. In cancer tissue, ERG protein expression showed a high rate of concordance with an underlying <italic>ERG</italic> rearrangement (91.5%). SLC45A3 showed a weaker expression in cancer as compared to benign tissue, which was pronounced in cases with <italic>SLC45A3‐ERG</italic> fusion. Importantly, SLC45A3 down regulation was significantly associated with shorter PSA‐free survival times. In contrast, TMPRSS2 was neither differentially expressed nor did it show a correlation between protein expression and rearrangement status. This study provides first evidence that the expression of SLC45A3 protein is down regulated through <italic>SLC45A3‐ERG</italic> fusion in prostate cancer. Moreover, these cases may represent a distinct molecular subclass of <italic>ERG</italic> rearranged prostate cancer with distinct clinical features. This study also confirms that ERG protein expression is predominantly found in prostate carcinomas with <italic>ERG</italic> gene rearrangement and does not occur in benign glands.</p> </abstract>