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  • Review Article
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The use of PCA3 in the diagnosis of prostate cancer

Abstract

Although the routine use of serum PSA testing has undoubtedly increased prostate cancer detection, one of its main drawbacks has been its lack of specificity, which results in a high negative biopsy rate. Consequently, a large population of men with chronically elevated serum PSA and one or more negative biopsies has emerged. More accurate tests are needed that can help identify which patients are at high risk of developing prostate cancer, and for whom repeat prostate biopsies are mandatory. To improve the specificity of prostate cancer diagnosis, prostate-cancer-specific markers, such as prostate cancer gene 3 (PCA3), are needed. The strong association between PCA3 mRNA overexpression and malignant transformation of prostate epithelium indicates its potential as a diagnostic biomarker. Quantification of PCA3 mRNA levels in urine was found to help predict the outcome of prostate biopsies. The intensive and time-consuming reverse-transcriptase polymerase chain reaction PCA3 urine test has been translated successfully into the fast and easy transcription-mediated amplification (TMA)-based PCA3 test. This test is the first RNA-based molecular diagnostic assay in body fluids for prostate cancer that is available to urologists. This Review describes the translation of the molecular marker PCA3 from the research laboratory to clinical practice.

Key Points

  • Unlike serum PSA, PCA3 is specific for prostate cancer and is not affected by prostate volume or other non-cancerous prostate conditions

  • The PCA3 score correlates with the result of a subsequent biopsy; in men with a high PCA3 score, the likelihood of a positive prostate biopsy is increased

  • Preliminary data demonstrate a correlation between PCA3 score and prostate cancer prognostic markers; therefore, PCA3 might identify men who have clinically insignificant prostate cancer and are candidates for active surveillance

  • The PCA3 test is the first fully translated molecular assay in body fluids that is a valuable tool in predicting biopsy outcome

  • Combining PCA3 as a continuous variable with other clinical or pathological factors or biomarkers (for example, TMPRSS2ERG gene fusions) will provide more-accurate prostate cancer diagnosis and prognosis

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Figure 1: Structure of the PCA3 transcription unit.
Figure 2: Sensitivity and specificity of PCA3 testing for detecting prostate cancer.
Figure 3: The correlation of PCA3 score (determined with the TMA-based PCA3 test) with the percentage of men with positive prostate biopsies.
Figure 4: PCA3 score and clinical relevance of prostate cancers.

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References

  1. Jemal, A. et al. Cancer statistics, 2008. CA Cancer J. Clin. 58, 71–96 (2008).

    Article  Google Scholar 

  2. Ferlay, J. et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann. Oncol. 18, 581–592 (2007).

    Article  CAS  Google Scholar 

  3. Roddam, A. W. et al. Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2–10 ng/ml: systematic review and meta-analysis. Eur. Urol. 4, 386–399 (2005).

    Article  Google Scholar 

  4. Hessels, D. et al. Applicability of biomarkers in the early diagnosis of prostate cancer. Expert Rev. Mol. Diagn. 4, 513–526 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Hessels, D. et al. Molecular Diagnostics in Prostate Cancer. EAU Update Series 3, 200–213 (2005).

    Article  Google Scholar 

  6. Bussemakers, M. J. et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 59, 5975–5979 (1999).

    CAS  PubMed  Google Scholar 

  7. de Kok, J. B. et al. DD3 (PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 62, 2695–2698 (2002).

    CAS  PubMed  Google Scholar 

  8. Hessels, D. et al. DD3 (PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur. Urol. 44, 8–15 (2003).

    Article  CAS  PubMed  Google Scholar 

  9. Schalken, J. A. et al. New targets for therapy in prostate cancer: differential display code 3 (DD3 [PCA3]), a highly prostate cancer-specific gene. Urology 62 (5 Suppl. 1), 34–43 (2003).

    Article  PubMed  Google Scholar 

  10. Iwakiri, J. et al. An analysis of urinary prostate specific antigen before and after radical prostatectomy: evidence for secretion of prostate specific antigen by the periurethral glands. J. Urol. 149, 783–786 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Meng, F. J. et al. The expression of a variant prostate-specific antigen in human prostate. Cancer Epidemiol. Biomarkers Prev. 11, 305–309 (2002).

    CAS  PubMed  Google Scholar 

  12. van Gils, M. P. et al. Molecular PCA3 diagnostics on prostatic fluid. Prostate 67, 881–887 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. van Gils, M. P. et al. The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; a Dutch multicenter validation of the diagnostic performance. Clin. Cancer Res. 13, 939–943 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Groskopf, J. et al. APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin. Chem. 52, 1089–1095 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Sokoll, L. J. et al. A multicenter evaluation of the PCA3 molecular urine test: pre-analytical effects, analytical performance, and diagnostic accuracy. Clin. Chim. Acta 389, 1–6 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Shappell, S. B. et al. PCA3 urine mRNA testing for prostate carcinoma: patterns of use by community urologists and assay performance in reference laboratory setting. Urology 73, 363–368 (2008).

    Article  PubMed  Google Scholar 

  17. Marks, L. S. et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 69, 532–535 (2007).

    Article  PubMed  Google Scholar 

  18. Deras, I. L. et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J. Urol. 179, 1587–1592 (2008).

    Article  PubMed  Google Scholar 

  19. Haese, A. et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur. Urol. 54, 1081–1088 (2008).

    Article  PubMed  Google Scholar 

  20. Ankerst, D. P. et al. Predicting prostate cancer risk through incorporation of prostate cancer gene 3. J. Urol. 180, 1303–1308 (2008).

    Article  PubMed  Google Scholar 

  21. Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644–648 (2005).

    Article  CAS  Google Scholar 

  22. Tomlins, S. A. et al. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 66, 3396–3400 (2006).

    Article  CAS  Google Scholar 

  23. Hessels, D. et al. Detection of TMPRSS2ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin. Cancer Res. 13, 5103–5108 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Laxman, B. et al. A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res. 68, 645–649 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. van Gils, M. P. et al. Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate 68, 1215–1222 (2008).

    Article  PubMed  Google Scholar 

  26. Nakanishi, H. et al. PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J. Urol. 179, 1804–1809 (2008).

    Article  PubMed  Google Scholar 

  27. Whitman, E. J. et al. PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J. Urol. 180, 1975–1978 (2008).

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Gerald W. Verhaegh (Experimental Urology, Radboud University Nijmegen Medical Centre) and Frank P. Smit (NovioGendix, Nijmegen) for their assistance in critically reading this manuscript.

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Correspondence to Jack A. Schalken.

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Competing interests

J. A. Schalken has been a speaker for Gen-Probe Inc.

NovioGendix is specialized in molecular diagnostics and offers services (e.g. the PCA3 test) to urologists and clinicians throughout Europe. Daphne Hessels is an employee of NovioGendix.

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Hessels, D., Schalken, J. The use of PCA3 in the diagnosis of prostate cancer. Nat Rev Urol 6, 255–261 (2009). https://doi.org/10.1038/nrurol.2009.40

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