The Ets-related gene fusions are among the most common molecular alterations in prostate cancer (PCa) and are detected in more than 50 % of PCas. Transmembrane protease serine 2 and Ets-related gene fusion (TMPRSS2-ERG) is the most frequently identified chimeric gene and has been associated with undifferentiated and invasive phenotypes. TMPRSS2-ERG has also been detected in prostate intraepithelial neoplasia (PIN) lesions and more rarely in benign prostatic hyperplasia (BPH) regions mainly in PCa-bearing glands. The possibility that the fusion TMPRSS2-ERG may be present in BPH samples in the absence of apparent PCa was addressed. Out of 115 BPH samples, three were found positive employing RT-PCR. The presence of the fusion gene was confirmed by FISH for these samples, and an additional four samples were found to carry the TMPRSS2-ERG fusion out of 43 tested by the later approach. The presence of the TMPRSS2-ERG fusion did not result in altered expression of 12 putative downstream targets. These findings indicate that TMPRSS2-ERG may or may not lead to PCa development.
Early diagnosis of prostate cancer and identification of new prognostic factors remain main issues in prostate cancer research. In this study, we sought to test a panel of cancer-specific markers in urine samples as an aid for early cancer diagnosis.Sedimented urine samples of 66 candidates for needle biopsy were tested. Real time-polymerase chain reaction (RT-PCR) was applied to detect the expression of transmembrane protease serine-2 and Ets-related gene fusion (TMPRSS2-ERG), Ets-related gene (ERG), prostate cancer antigen-3 (PCA3), and serine peptidase inhibitor kazal type-1 (SPINK1) transcripts. For testing of the methylation status of Glutahione S-tranferase P (GSTP1) and Ras association domain family member-1(RASSF1A) promoter region, methylation-specific PCR (MSP-PCR) was applied.Among the tested parameters, the presence of TMPRSS2-ERG (OR=9.044, 95% CI=2.207-37.066, p=0.002), as well as a positive test result for PCA3 (OR=7.549, 95% CI=1,858-30,672, p=0.005) were associated with the subsequent diagnosis of prostate cancer. A multivariable logistic regression including all the significantly associated variables [prostate-specific antigen (PSA), digital rectal examination (DRE), TMPRSS2-ERG and PCA3], yielded a model with area under the receiver-operating characteristic curve (AUC) =0.894 (95% CI=0.772-1.00).A multiplexed quantitative PCR analysis on sedimented urine, in conjunction with the results of serum PSA levels and DRE, has the potential to accurately foresee subsequent needle biopsy outcomes. On the basis of the above, algorithms may be designed to guide decisions for needle biopsy.
