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Purpose: Our aim was to assess the frequency of ERG overexpression and TMPRSS2 :ERG rearrangement in prostate cancer and their association with clinicopathologic variables and outcome. Experimental Design: The presence of the TMPRSS2 :ERG rearrangement was studied by reverse transcription-PCR and fluorescence in situ hybridization in 19 prostate cancer xenografts and 7 prostate cancer cell lines.The expression of ERG was studied in the xenografts and cell lines and in 49 freshly frozen clinical prostate samples by quantitative reverse transcription-PCR. The frequency of the TMPRSS2 :ERG fusion in clinical prostate cancer (n = 253) on tissue microarrays was assessed by three-color fluorescence in situ hybridization. Results: Seven of 19 (37%) of the xenografts overexpressed ERG and had TMPRSS2 :ERG rearrangement. Two xenografts, representing small cell carcinomas, also contained the fusion but did not express ERG. In clinical tumor specimens, the overexpression of ERG was associated with the rearrangement (P = 0.0019). Fifty of 150 (33%) of the prostatectomy specimens and 28 of 76 (37%) of the hormone-refractory prostate cancers on the tissue microarrays carried the TMPRSS2 :ERG rearrangement. It was associated with longer progression-free survival in patients treated by prostatectomy (P = 0.019), and according to multivariate analysis, it was an independent predictor of favorable outcome (relative risk, 0.54; 95% confidence interval, 0.30-0.98). The fusion was not associated with Gleason score, pT stage, diagnostic prostatespecific antigen, or cell proliferation activity in prostatectomy specimens nor with the AR gene amplification in hormone-refractory tumors. Conclusions: The TMPRSS2 :ERG rearrangement can be found in about one third of prostate cancers. A subgroup of prostate cancer patients with a good prognosis may be identified by the rearrangement.Recent studies suggest that >50% of prostate tumors may carry a chromosomal rearrangement on chromosome 21q22 (1 -4). The genes involved are the androgen-inducible TMPRSS2 (transmembrane protease, serine 2) and an ETS family transcription factor, ERG [v-ets erythroblastosis virus E26 oncogene like (avian)]. As a result of the rearrangement, the expression of ERG becomes androgen regulated.TMPRSS2 is highly expressed in normal and neoplastic prostate in an androgen-dependent manner (5, 6). Its significance is unknown, as knockout mice show a normal phenotype, indicating that the gene is redundant (7). ERG is a transcription factor often involved in oncogenic translocations in Ewing's sarcoma and myeloid leukemias (8). It has been shown to interact with a histone H3-specific methyltransferase (ESET) and may hence participate in the epigenetic silencing of downstream target genes (9).The genomic breakpoints and the fusion transcripts of TMPRSS2:ERG are not uniform (1 -3, 10 -14). To date, f20 different variants of TMPRSS2:ERG have been described. The two most common variants (TMPRSS2 exon1:ERG exon4/5) presumably produce a full-length, functional ERG and h...

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Prolactin is widely expressed in different tissues, and it is presumed to have both local and systemic actions. In males it is known to influence reproductive functions but the significance and mechanisms of prolactin action in male accessory reproductive tissues are poorly understood. Here we show that prolactin acts as a direct growth and differentiation factor for human prostate, as measured by changes in DNA synthesis and epithelial morphology of organ cultures.

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