title: Loss of SLC45A3 protein (prostein) expression in prostate cancer is associated with SLC45A3-ERG gene rearrangement and an unfavorable clinical course.
abstract: The majority of prostate cancer harbors recurrent gene fusions involving ETS transcription factors, most commonly ERG. The second most common 5' fusion partner after TMPRSS2 is SLC45A3. 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 SLC45A3 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 ERG rearrangement (91.5%). SLC45A3 showed a weaker expression in cancer as compared to benign tissue, which was pronounced in cases with SLC45A3-ERG 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 SLC45A3-ERG fusion in prostate cancer. Moreover, these cases may represent a distinct molecular subclass of ERG rearranged prostate cancer with distinct clinical features. This study also confirms that ERG protein expression is predominantly found in prostate carcinomas with ERG gene rearrangement and does not occur in benign glands.
authors: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: Sven
authors: S
authors: Perner
authors: Niels J
authors: NJ
authors: Rupp
authors: Martin
authors: M
authors: Braun
authors: Mark A
authors: MA
authors: Rubin
authors: Holger
authors: H
authors: Moch
authors: Manfred
authors: M
authors: Dietel
authors: Nicolas
authors: N
authors: Wernert
authors: Klaus
authors: K
authors: Jung
authors: Carsten
authors: C
authors: Stephan
authors: Glen
authors: G
authors: Kristiansen
mesh_terms: D015536:Down-Regulation; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009004:Monosaccharide Transport Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D015514:Oncogene Proteins, Fusion; C551031:SLC45a3 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human