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.