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Background: The prostate cancer gene 3 (PCA3) and TMPRSS2:ERG gene fusion are promising prostate cancer (PCa) specific biomarkers. Our aim was to simultaneously quantify the expression levels of PCA3 and TMPRSS2:ERG in a panel of benign prostatic hyperplasia (BPH), normal prostate adjacent to PCa (NP) and PCa tissue samples, to provide a rational basis for the understanding of the false-positive and false-negative results of the urine assays., Methods: The tissue samples were carefully histopathologically characterized to obtain homogeneous groups. The mRNA was isolated, transcribed into cDNA and the relative expressions of PCA3 and TMPRSS2:ERG were measured using a quantitative real-time polymerase chain reaction. The expression levels of PCA3 and TMPRSS2:ERG were compared between the different groups., Results: We included 48 BPH, 32 NP, and 48 PCa. The PCA3 expression levels progressively increased from BPH to NP (3 times) and finally to PCa (30 times). There were one false-positive sample and seven false-negative samples. The TMPRSS2:ERG gene fusion was found in 8.3% of the BPH, 15.6% of the NP, and 50% of the PCa samples. The use of TMPRSS2:ERG in the PCA3 negative cases allowed diagnosis of four of the seven false-negative samples and added one false-positive, but we had to define a cut-off value to avoid eight false-positive results., Conclusions: Considering tissue expression of the markers, most of the false-negative results of the PCA3 test were corrected by TMPRSS2:ERG (57%) and the combination of both had a higher sensitivity for PCa diagnosis. Some of the control samples did express TMPRSS2:ERG and a cut-off value had to be defined to avoid false-positive results., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Chronic prostatic inflammation could be a central mechanism in benign prostatic hyperplasia (BPH) progression. Currently, the histological examination of prostate biopsies remains the only way to diagnose prostatic inflammation. Our objective was to find new noninvasive biomarkers for the diagnosis of prostatic inflammation., Methods: Ninety BPH samples were investigated in two steps. First, a hypothesis was generated using a profiling procedure with a panel of 96 genes on an initial set of 30 samples. Then, the candidate biomarkers were validated on a large number of samples (n = 90). Gene expression was compared with the histological prostatic inflammation score based on the density and the confluence of lymphoid nodules. Finally, protein transcripts of the candidate biomarkers were investigated in urine samples and compared with clinical data., Results: Of the 96 genes, nine were significantly correlated with the inflammation score on the initial set of patients. Four of them were validated on the complete set of patients: CCR7, CD40LG, CTLA4, and ICOS. ICOS and CTLA4 protein levels were readily measured in urine samples using a conventional ELISA procedure. High-ICOS expression in urine was associated with a higher post-void residual and a lower maximum urinary flow rate., Conclusions: Four genes were significantly upregulated at the mRNA level in the prostate tissue of patients with severe inflammation score. Two proteins were measured in urine samples, and were associated with maximum uroflowmetry and post-void residual. A prospective clinical study is needed to confirm their clinical relevance., (Copyright © 2011 Wiley-Liss, Inc.)

Background: PCA3 is one of the most prostate cancer (PrCa)-specific markers described so far. Recently, a new genomic structure of PCA3 as well as new flanking and overlapping gene transcripts has been identified. Furthermore, a co-regulation of PCA3 and its overlapping gene PRUNE2(BMCC1) has been suggested. Our aim was to assess the diagnostic performance of a new PCA3 isoform (PCA3-TS4) and to study the interactions between PCA3 and BMCC1 in PrCa., Methods: We used SYBR Green quantitative (q)PCR with specific primers to compare PCA3 and BMCC1 expression of normal versus tumor tissue of human prostate. PCA3-TS4 plasmid was created to calculate the absolute amounts of PCA3 transcripts. The androgen regulation of PCA3 and BMCC1 expression was studied in LNCaP and 22Rv1 cells stimulated with 5alpha-dihydrotestosterone., Results: We have not found any relevant diagnostic advantage of the PCA3-TS4 isoform over the "classical" PCA3 isoform in our group of PrCa patients. Additionally, PCA3-TS4 appears to be only a minor PCA3 transcript. We were also unable to confirm the hypothesis that BMCC1 isoforms are androgen-induced in vitro., Conclusions: Despite the presence of the recently identified marginal PCA3 transcripts in human PrCa, the previously described major PCA3 isoform still constitutes the best target for diagnostic purposes. PCA3 and BMCC1 are overlapping genes in reverse orientation that do not appear to be co-regulated., ((c) 2009 Wiley-Liss, Inc.)

Purpose: PCA3 urine tests have shown to improve the specificity in prostate cancer (PCa) diagnosis, and have thus the potential to reduce the number of unnecessary prostate biopsies and to predict repeat biopsy outcomes. In this study, PCA3 was correlated with clinical stage, biopsy Gleason score (GS), radical prostatectomy GS, tumor volume, and pathological stage to assess its potential as predictor of PCa aggressiveness., Methods: In this study, 351 men admitted for prostate biopsies based on serum PSA levels >3 ng/ml, an abnormal DRE, and/or a family history of PCa were included. Post-DRE urinary sediments from 336 men were tested using a transcription-mediated amplification-based PCA3 test, and assay results were correlated with clinical stage and biopsy GS. In a sub-cohort of 70 men who underwent radical prostatectomy, the PCA3 values were correlated to their radical prostatectomy GS, tumor volume, and pathological stage., Results: In this patient cohort we could not find a correlation between clinical stage, biopsy GS, radical prostatectomy GS, tumor volume, and pathological stage., Conclusions: The predictive value of PCA3 for PCa aggressiveness features as reported in earlier studies cannot be confirmed in our study. Experimental differences (urine sediments vs. whole urine) and cohort may explain this. The exact place of PCA3 as prognostic test for PCa remains the subject of investigation., ((c) 2009 Wiley-Liss, Inc.)

Background: Dutasteride is commonly used in patients that are also at risk for prostate cancer (PCa). Therefore, the influence of dutasteride on PCa markers has to be studied. To date, only the effect of dutasteride on serum prostate-specific antigen (PSA) has been studied. This was the first study to investigate the effect of dutasteride on the new PCa marker PCA3, longitudinally and in a dose dependent manner., Methods: From April 25, 2005 to October 31, 2006, 16 subjects with benign prostatic hyperplasia (BPH) and 9 subjects with clinically localized PCa were enrolled at the urological outpatient clinics of one university hospital and one community hospital. Eight subjects with BPH and five with PCa received 0.5 mg dutasteride once daily for 3 months, eight with BPH and four with PCa received 3.5 mg. No subjects were withdrawn because of adverse effects., Results: In all four groups both 0.5 and 3.5 mg dutasteride had a variable effect on the PCA3 score. In contrast, its other effects were consistent as it rapidly reduced serum DHT by >or=90%, over time increased serum T by 20-30%, over time halved serum PSA and decreased prostate volume by 10-16%., Conclusions: In this exploratory/pilot study the effect of dutasteride on the PCA3 score was variable. This should be taken into account while using PCA3 in diagnostics. As this study was exploratory, the influence of androgen-deprivation therapy on the PCA3 score should be analyzed further.

Background: Due to the drawbacks of serum prostate-specific antigen, there is an ongoing search for new diagnostic and prognostic prostate cancer (PCa) markers. PCA3 has proven to be of value in the diagnosis of PCa. However, so far few attempts have been made to investigate the prognostic value of PCA3. Our objective was to further investigate the prognostic value of PCA3., Methods: In this study we correlated the PCA3 score in urinary sediments after digital rectal examination in 62 men with the classical prognostic parameters assessed in radical prostatectomy specimens (i.e. Gleason score, pathological tumor stage and total tumor volume) and moreover, with the expression of three immunohistochemical markers for PCa biological aggressiveness (i.e. E-cadherin, alpha-catenin and EZH2). The results from this study serve as a reflection on and a valuable adjunct to recently published results., Results: We did not find a significant correlation of the PCA3 score with the classical prognostic parameters assessed in radical prostatectomy specimens or the expression of the immunohistochemical markers for PCa biological aggressiveness. However, we did observe a trend for a higher PCA3 score in significant PCa versus insignificant PCa, aberrant E-cadherin staining versus normal E-cadherin staining and increased EZH2 staining versus normal EZH2 staining., Conclusions: In this study we could not prove the prognostic value of PCA3. Further research with large numbers of men and adequate follow-up is needed to provide a definitive answer to the question if PCA3 is not only a diagnostic but also a prognostic PCa marker., (Copyright (c) 2008 Wiley-Liss, Inc.)

Background: The PCA3 test on urine can improve specificity in prostate cancer (PCa) diagnosis and could prevent unnecessary prostate biopsies. In this study, we evaluated the PCA3 test on prostatic fluid and compared this with the PCA3 test on urine in a clinical research setting., Methods: Prostatic fluid and urine samples from 67 men were collected following digital rectal examination (DRE). The sediments were analyzed using the quantitative APTIMA PCA3 test. The results were compared with prostate biopsy results., Results: Using a PCA3 score of 66 as a cut-off value, the test on prostatic fluid had 65% sensitivity for the detection of PCa, 82% specificity and a negative predictive value of 82%. At a cut-off value of 43, the test on urine had 61% sensitivity, 80% specificity and a negative predictive value of 80%., Conclusions: The PCA3 test can be performed on both urine and prostatic fluid in the diagnosis of PCa with comparable results., (Copyright 2007 Wiley-Liss, Inc.)

Background: Cross-contamination is a persistent problem in the establishment and maintenance of mammalian cell lines. The observation that the cell lines PC-3, ALVA-31, and PPC-1 all have a homozygous deletion of the alpha-catenin gene prompted us to investigate the uniqueness of these and several other widely used prostate carcinoma cell lines., Methods: The genetic backgrounds of the putative human prostate cell lines (ALVA-31, ALVA-41, BPH-1, DU 145, JCA-1, LAPC-4, LNCaP, NCI-H660, ND-1, PC-3, PC-3MM2, PC-346C, PPC-1, and TSU-Pr1) were analyzed by cytogenetics, mutation analysis, and DNA profiling., Results: Similarities between several groups of cell lines were found. ALVA-31, ALVA-41, PC-3, PC-3MM2, and PPC-1 all have a deletion of a C in codon 138 of the p53 gene and show almost identical DNA profiles. The ND-1 cell line has two p53 mutations that are identical to the mutations found in DU 145. These two cell lines also share a high number of structural chromosomal abnormalities and nearly identical DNA profiles. The cell lines TSU-Pr1 and JCA-1 share an identical p53 mutation in exon 5 and identical DNA profiles., Conclusions: Several widely used prostate carcinoma cell lines apparently have identities in common. The knowledge that some of these cell lines are derivatives of one another prompts re-evaluation of previously obtained results.