Biomarkers for Prostate Cancer

  • S. Dijkstra
  • R. J. Hendriks
  • G. H. J. M. Leyten
  • P. F. A. Mulders
  • J. A. Schalken
Chapter
First Online:

Abstract

In the last decade, revolutionary advancements in molecular profiling technologies resulted in new diagnostic algorithms. These advances have marked the beginning of a new era for modern medicine: precision medicine. Biomarkers are important tools in individualized medicine, to accurately predict the biological behaviour, and therapy response for well-stratified/homogeneous groups of patients. This chapter focuses on established biomarkers for prostate cancer and promising novel biomarkers: arranged by the diagnostic substrate used, that is, tissue markers, blood markers and urine markers. Many new biomarkers are ready for ‘prime time’, yet it needs carefully designed studies to test the exact clinical positioning. The STARD (STAndards for Reporting of Diagnostic accuracy) statement and the REMARK guidelines (Reporting Recommendations for Tumor Marker Prognostic Studies) are two initiatives that are important steps forward in improving the quality of tumour marker studies.

Keywords

Prostate Cancer Radical Prostatectomy Gleason Score Digital Rectal Examination Prostate Cancer Prevention Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Aaltomaa S, Lipponen P, Vesalainen S, Ala-Opas M, Eskelinen M, Syrjanen K. Value of Ki-67 immunolabelling as a prognostic factor in prostate cancer. Eur Urol. 1997;32(4):410–5.PubMedGoogle Scholar
  2. 2.
    Aggarwal R, Zhang T, Small EJ, Armstrong AJ. Neuroendocrine prostate cancer: subtypes, biology, and clinical outcomes. J Natl Compr Canc Netw. 2014;12(5):719–26.PubMedGoogle Scholar
  3. 3.
    Anai S, Goodison S, Shiverick K, Iczkowski K, Tanaka M, Rosser CJ. Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. Hum Gene Ther. 2006;17(10):975–84. doi: 10.1089/hum.2006.17.975.PubMedCrossRefGoogle Scholar
  4. 4.
    Ang JE, Olmos D, de Bono JS. CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer. Br J Cancer. 2009;100(5):671–5. doi: 10.1038/sj.bjc.6604904.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Ankerst DP, Groskopf J, Day JR, Blase A, Rittenhouse H, Pollock BH, et al. Predicting prostate cancer risk through incorporation of prostate cancer gene 3. J Urol. 2008;180(4):1303–8. doi: 10.1016/j.juro.2008.06.038; discussion 8.PubMedCrossRefGoogle Scholar
  6. 6.
    Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014;371(11):1028–38. doi: 10.1056/NEJMoa1315815.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Arlen PM, Bianco F, Dahut WL, D’Amico A, Figg WD, Freedland SJ, et al. Prostate Specific Antigen Working Group guidelines on prostate specific antigen doubling time. J Urol. 2008;179(6):2181–5. doi: 10.1016/j.juro.2008.01.099; discussion 5–6.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Attard G, Clark J, Ambroisine L, Mills IG, Fisher G, Flohr P, et al. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer. Br J Cancer. 2008;99(2):314–20. doi: 10.1038/sj.bjc.6604472.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Auprich M, Chun FK, Ward JF, Pummer K, Babaian R, Augustin H, et al. Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging. Eur Urol. 2011;59(1):96–105. doi: 10.1016/j.eururo.2010.10.024.PubMedCrossRefGoogle Scholar
  10. 10.
    Auprich M, Haese A, Walz J, Pummer K, de la Taille A, Graefen M, et al. External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome. Eur Urol. 2010;58(5):727–32. doi: 10.1016/j.eururo.2010.06.038.PubMedCrossRefGoogle Scholar
  11. 11.
    Barry MJ. Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. N Engl J Med. 2001;344(18):1373–7. doi: 10.1056/NEJM200105033441806.PubMedCrossRefGoogle Scholar
  12. 12.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.PubMedCrossRefGoogle Scholar
  13. 13.
    Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33. doi: 10.1016/j.cell.2009.01.002.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Becker C, Piironen T, Pettersson K, Hugosson J, Lilja H. Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater. Urology. 2000;55(5):694–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Bedolla R, Prihoda TJ, Kreisberg JI, Malik SN, Krishnegowda NK, Troyer DA, et al. Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression and Akt activation. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(13):3860–7. doi: 10.1158/1078-0432.CCR-07-0091.CrossRefGoogle Scholar
  16. 16.
    Benson MC, Whang IS, Pantuck A, Ring K, Kaplan SA, Olsson CA, et al. Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. J Urol. 1992;147(3 Pt 2):815–6.PubMedGoogle Scholar
  17. 17.
    Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW. Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol. 1996;156(3):1064–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. doi: 10.1067/mcp.2001.113989.CrossRefGoogle Scholar
  19. 19.
    Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994;1198(1):11–26.PubMedGoogle Scholar
  20. 20.
    Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14(11):1271–7. doi: 10.1038/nm.1880.PubMedCrossRefGoogle Scholar
  21. 21.
    Borer JG, Sherman J, Solomon MC, Plawker MW, Macchia RJ. Age specific prostate specific antigen reference ranges: population specific. J Urol. 1998;159(2):444–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Borre M, Bentzen SM, Nerstrom B, Overgaard J. Tumor cell proliferation and survival in patients with prostate cancer followed expectantly. J Urol. 1998;159(5):1609–14. doi: 10.1097/00005392-199805000-00054.PubMedCrossRefGoogle Scholar
  23. 23.
    Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem. 2003;49(1):7–18.PubMedCrossRefGoogle Scholar
  24. 24.
    Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015;351:h5527. doi: 10.1136/bmj.h5527.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Bradford TJ, Tomlins SA, Wang X, Chinnaiyan AM. Molecular markers of prostate cancer. Urol Oncol. 2006;24(6):538–51. doi: 10.1016/j.urolonc.2006.07.004.PubMedCrossRefGoogle Scholar
  26. 26.
    Brawer MK, Aramburu EA, Chen GL, Preston SD, Ellis WJ. The inability of prostate specific antigen index to enhance the predictive the value of prostate specific antigen in the diagnosis of prostatic carcinoma. J Urol. 1993;150(2 Pt 1):369–73.PubMedGoogle Scholar
  27. 27.
    Breuer RH, Snijders PJ, Smit EF, Sutedja TG, Sewalt RG, Otte AP, et al. Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis. Neoplasia. 2004;6(6):736–43. doi: 10.1593/neo.04160.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P, et al. Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol. 1996;178(4):437–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 1999;59(23):5975–9.PubMedGoogle Scholar
  30. 30.
    Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004;101(32):11755–60. doi: 10.1073/pnas.0404432101.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Cantiello F, Russo GI, Cicione A, Ferro M, Cimino S, Favilla V, et al. PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance. World J Urol. 2015. doi: 10.1007/s00345-015-1643-z.Google Scholar
  32. 32.
    Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008;27(58):7274–84. doi: 10.1038/onc.2008.333.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Catalona WJ, Bartsch G, Rittenhouse HG, Evans CL, Linton HJ, Amirkhan A, et al. Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml. J Urol. 2003;170(6 Pt 1):2181–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bangma CH, et al. A multicenter study of [−2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range. J Urol. 2011;185(5):1650–5. doi: 10.1016/j.juro.2010.12.032.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA. 1998;279(19):1542–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Cattoretti G, Becker MH, Key G, Duchrow M, Schluter C, Galle J, et al. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992;168(4):357–63. doi: 10.1002/path.1711680404.PubMedCrossRefGoogle Scholar
  37. 37.
    Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 2007;8(2):93–103. doi: 10.1038/nrg1990.PubMedCrossRefGoogle Scholar
  38. 38.
    Chen H, Tu SW, Hsieh JT. Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J Biol Chem. 2005;280(23):22437–44. doi: 10.1074/jbc.M501379200.PubMedCrossRefGoogle Scholar
  39. 39.
    Chun FK, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, et al. Prostate cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram. Eur Urol. 2009;56(4):659–67. doi: 10.1016/j.eururo.2009.03.029.PubMedCrossRefGoogle Scholar
  40. 40.
    Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(19):3213–21. doi: 10.1200/JCO.2007.15.8923.CrossRefGoogle Scholar
  41. 41.
    Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol/ESMO. 2009;20(7):1223–9. doi: 10.1093/annonc/mdn786.CrossRefGoogle Scholar
  42. 42.
    Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91. doi: 10.1056/NEJMoa040766.PubMedCrossRefGoogle Scholar
  43. 43.
    Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(7):1420–30. doi: 10.1200/JCO.2005.08.140.CrossRefGoogle Scholar
  44. 44.
    Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14. doi: 10.1038/nrg2634.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Cullen J, Rosner IL, Brand TC, Zhang N, Tsiatis AC, Moncur J, et al. A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur Urol. 2015;68(1):123–31. doi: 10.1016/j.eururo.2014.11.030.PubMedCrossRefGoogle Scholar
  46. 46.
    Cuzick J, Stone S, Fisher G, Yang ZH, North BV, Berney DM, et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br J Cancer. 2015;113(3):382–9. doi: 10.1038/bjc.2015.223.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    D’Amico AV, Roehrborn CG. Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol. 2007;8(1):21–5. doi: 10.1016/S1470-2045(06)70981-0.PubMedCrossRefGoogle Scholar
  48. 48.
    Danila DC, Heller G, Gignac GA, Gonzalez-Espinoza R, Anand A, Tanaka E, et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(23):7053–8. doi: 10.1158/1078-0432.CCR-07-1506.CrossRefGoogle Scholar
  49. 49.
    de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(19):6302–9. doi: 10.1158/1078-0432.CCR-08-0872.CrossRefGoogle Scholar
  50. 50.
    de la Taille A, Irani J, Graefen M, Chun F, de Reijke T, Kil P, et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol. 2011;185(6):2119–25. doi: 10.1016/j.juro.2011.01.075.PubMedCrossRefGoogle Scholar
  51. 51.
    Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005;105(7):2640–53. doi: 10.1182/blood-2004-08-3097.PubMedCrossRefGoogle Scholar
  52. 52.
    Demichelis F, Fall K, Perner S, Andren O, Schmidt F, Setlur SR, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene. 2007;26(31):4596–9. doi: 10.1038/sj.onc.1210237.PubMedCrossRefGoogle Scholar
  53. 53.
    Deras IL, Aubin SM, Blase A, Day JR, Koo S, Partin AW, et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol. 2008;179(4):1587–92. doi: 10.1016/j.juro.2007.11.038.PubMedCrossRefGoogle Scholar
  54. 54.
    Dijkstra S, Leyten GH, Jannink SA, de Jong H, Mulders PF, van Oort IM, et al. KLK3, PCA3, and TMPRSS2-ERG expression in the peripheral blood mononuclear cell fraction from castration-resistant prostate cancer patients and response to docetaxel treatment. Prostate. 2014;74(12):1222–30. doi: 10.1002/pros.22839.PubMedCrossRefGoogle Scholar
  55. 55.
    Duffy MJ. Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers. Biochem Soc Trans. 2002;30(2):207–10. 10.1042/.PubMedCrossRefGoogle Scholar
  56. 56.
    Eeles R, Goh C, Castro E, Bancroft E, Guy M, Al Olama AA, et al. The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol. 2014;11(1):18–31. doi: 10.1038/nrurol.2013.266.PubMedCrossRefGoogle Scholar
  57. 57.
    Efstathiou JA, Chen MH, Catalona WJ, McLeod DG, Carroll PR, Moul JW, et al. Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality. Urology. 2006;68(2):342–7. doi: 10.1016/j.urology.2006.02.030.PubMedCrossRefGoogle Scholar
  58. 58.
    Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013;8(6):e66855. doi: 10.1371/journal.pone.0066855.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Fabris L, Ceder Y, Chinnaiyan AM, Jenster GW, Sorensen KD, Tomlins S, et al. The potential of microRNAs as prostate cancer biomarkers. Eur Urol. 2016. doi: 10.1016/j.eururo.2015.12.054.PubMedGoogle Scholar
  60. 60.
    Ferraldeschi R, Nava Rodrigues D, Riisnaes R, Miranda S, Figueiredo I, Rescigno P, et al. PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol. 2015;67(4):795–802. doi: 10.1016/j.eururo.2014.10.027.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    FitzGerald LM, Agalliu I, Johnson K, Miller MA, Kwon EM, Hurtado-Coll A, et al. Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer. 2008;8:230. doi: 10.1186/1471-2407-8-230.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Font-Tello A, Juanpere N, de Muga S, Lorenzo M, Lorente JA, Fumado L, et al. Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels. Prostate. 2015;75(11):1216–26. doi: 10.1002/pros.23004.PubMedCrossRefGoogle Scholar
  63. 63.
    Fossati N, Buffi NM, Haese A, Stephan C, Larcher A, McNicholas T, et al. Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer: results from a multicentric European prospective study. Eur Urol. 2015;68(1):132–8. doi: 10.1016/j.eururo.2014.07.034.PubMedCrossRefGoogle Scholar
  64. 64.
    Fowler Jr JE, Bigler SA, Kilambi NK, Land SA. Relationships between prostate-specific antigen and prostate volume in black and white men with benign prostate biopsies. Urology. 1999;53(6):1175–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, Ciafre SA, et al. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem. 2007;282(32):23716–24. doi: 10.1074/jbc.M701805200.PubMedCrossRefGoogle Scholar
  66. 66.
    Goldkorn A, Ely B, Quinn DI, Tangen CM, Fink LM, Xu T, et al. Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(11):1136–42. doi: 10.1200/JCO.2013.51.7417.CrossRefGoogle Scholar
  67. 67.
    Gopalan A, Leversha MA, Satagopan JM, Zhou Q, Al-Ahmadie HA, Fine SW, et al. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res. 2009;69(4):1400–6. doi: 10.1158/0008-5472.CAN-08-2467.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Groskopf J, Aubin SM, Deras IL, Blase A, Bodrug S, Clark C, et al. APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem. 2006;52(6):1089–95. doi: 10.1373/clinchem.2005.063289.PubMedCrossRefGoogle Scholar
  69. 69.
    Guazzoni G, Nava L, Lazzeri M, Scattoni V, Lughezzani G, Maccagnano C, et al. Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting. Eur Urol. 2011;60(2):214–22. doi: 10.1016/j.eururo.2011.03.052.PubMedCrossRefGoogle Scholar
  70. 70.
    Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466(7308):835–40. doi: 10.1038/nature09267.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Gutman AB, Gutman EB. An “acid” phosphatase occurring in the serum of patients with metastasizing carcinoma of the prostate gland. J Clin Invest. 1938;17(4):473–8. doi: 10.1172/JCI100974.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol. 2008;54(5):1081–8. doi: 10.1016/j.eururo.2008.06.071.PubMedCrossRefGoogle Scholar
  73. 73.
    Haese A, Graefen M, Steuber T, Becker C, Pettersson K, Piironen T, et al. Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ-confined from locally-advanced prostate cancer in total PSA-levels below 10 ng/ml. Prostate. 2001;49(2):101–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Han B, Mehra R, Dhanasekaran SM, Yu J, Menon A, Lonigro RJ, et al. A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer. Cancer Res. 2008;68(18):7629–37. doi: 10.1158/0008-5472.CAN-08-2014.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31. doi: 10.1038/nrg1379.PubMedCrossRefGoogle Scholar
  76. 76.
    Herrala AM, Porvari KS, Kyllonen AP, Vihko PT. Comparison of human prostate specific glandular kallikrein 2 and prostate specific antigen gene expression in prostate with gene amplification and overexpression of prostate specific glandular kallikrein 2 in tumor tissue. Cancer. 2001;92(12):2975–84.PubMedCrossRefGoogle Scholar
  77. 77.
    Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol. 2003;44(1):8–15; discussion −6.PubMedCrossRefGoogle Scholar
  78. 78.
    Hessels D, Smit FP, Verhaegh GW, Witjes JA, Cornel EB, Schalken JA. Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(17):5103–8. doi: 10.1158/1078-0432.CCR-07-0700.CrossRefGoogle Scholar
  79. 79.
    Hessels D, van Gils MP, van Hooij O, Jannink SA, Witjes JA, Verhaegh GW, et al. Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate. 2010;70(1):10–6. doi: 10.1002/pros.21032.PubMedCrossRefGoogle Scholar
  80. 80.
    Huang H, Cheville JC, Pan Y, Roche PC, Schmidt LJ, Tindall DJ. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem. 2001;276(42):38830–6. doi: 10.1074/jbc.M103632200.PubMedCrossRefGoogle Scholar
  81. 81.
    Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database Syst Rev. 2013;1:CD004720. doi: 10.1002/14651858.CD004720.pub3.Google Scholar
  82. 82.
    Ioannidis JP, Castaldi P, Evangelou E. A compendium of genome-wide associations for cancer: critical synopsis and reappraisal. J Natl Cancer Inst. 2010;102(12):846–58. doi: 10.1093/jnci/djq173.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Josson S, Sung SY, Lao K, Chung LW, Johnstone PA. Radiation modulation of microRNA in prostate cancer cell lines. Prostate. 2008;68(15):1599–606. doi: 10.1002/pros.20827.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Karazanashvili G, Abrahamsson PA. Prostate specific antigen and human glandular kallikrein 2 in early detection of prostate cancer. J Urol. 2003;169(2):445–57. doi: 10.1097/01.ju.0000047085.42539.1c.PubMedCrossRefGoogle Scholar
  85. 85.
    Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A. 2003;100(20):11606–11. doi: 10.1073/pnas.1933744100.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Klein EA, Yousefi K, Haddad Z, Choeurng V, Buerki C, Stephenson AJ, et al. A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. Eur Urol. 2015;67(4):778–86. doi: 10.1016/j.eururo.2014.10.036.PubMedCrossRefGoogle Scholar
  87. 87.
    Koyanagi M, Baguet A, Martens J, Margueron R, Jenuwein T, Bix M. EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells. J Biol Chem. 2005;280(36):31470–7. doi: 10.1074/jbc.M504766200.PubMedCrossRefGoogle Scholar
  88. 88.
    Kumaresan K, Kakkar N, Verma A, Mandal AK, Singh SK, Joshi K. Diagnostic utility of alpha-methylacyl CoA racemase (P504S) & HMWCK in morphologically difficult prostate cancer. Diagn Pathol. 2010;5:83. doi: 10.1186/1746-1596-5-83.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Laxman B, Tomlins SA, Mehra R, Morris DS, Wang L, Helgeson BE, et al. Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia. 2006;8(10):885–8. doi: 10.1593/neo.06625.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Leyten GH, Hessels D, Jannink SA, Smit FP, de Jong H, Cornel EB, et al. Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur Urol. 2014;65(3):534–42. doi: 10.1016/j.eururo.2012.11.014.PubMedCrossRefGoogle Scholar
  91. 91.
    Leyten GH, Hessels D, Smit FP, Jannink SA, de Jong H, Melchers WJ, et al. Identification of a candidate gene panel for the early diagnosis of prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2015;21(13):3061–70. doi: 10.1158/1078-0432.CCR-14-3334.CrossRefGoogle Scholar
  92. 92.
    Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Lilja H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest. 1985;76(5):1899–903. doi: 10.1172/JCI112185.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Lilja H, Ulmert D, Bjork T, Becker C, Serio AM, Nilsson JA, et al. Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(4):431–6. doi: 10.1200/JCO.2006.06.9351.CrossRefGoogle Scholar
  95. 95.
    Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 2008;8(4):268–78. doi: 10.1038/nrc2351.PubMedCrossRefGoogle Scholar
  96. 96.
    Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 2008;14(3):417–24. doi: 10.1261/rna.874808.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Linton HJ, Marks LS, Millar LS, Knott CL, Rittenhouse HG, Mikolajczyk SD. Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease. Clin Chem. 2003;49(2):253–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Lintula S, Stenman J, Bjartell A, Nordling S, Stenman UH. Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissue. Prostate. 2005;63(4):324–9. doi: 10.1002/pros.20194.PubMedCrossRefGoogle Scholar
  99. 99.
    Loeb S. Guideline of guidelines: prostate cancer screening. BJU Int. 2014;114(3):323–5. doi: 10.1111/bju.12854.PubMedGoogle Scholar
  100. 100.
    Loeb S, Bruinsma SM, Nicholson J, Briganti A, Pickles T, Kakehi Y, et al. Active surveillance for prostate cancer: a systematic review of clinicopathologic variables and biomarkers for risk stratification. Eur Urol. 2015;67(4):619–26. doi: 10.1016/j.eururo.2014.10.010.PubMedCrossRefGoogle Scholar
  101. 101.
    Loeb S, Catalona WJ. The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol. 2014;6(2):74–7. doi: 10.1177/1756287213513488.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Loeb S, Roehl KA, Antenor JA, Catalona WJ, Suarez BK, Nadler RB. Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old. Urology. 2006;67(2):316–20. doi: 10.1016/j.urology.2005.08.040.PubMedCrossRefGoogle Scholar
  103. 103.
    Lundwall A, Clauss A, Olsson AY. Evolution of kallikrein-related peptidases in mammals and identification of a genetic locus encoding potential regulatory inhibitors. Biol Chem. 2006;387(3):243–9. doi: 10.1515/BC.2006.032.PubMedCrossRefGoogle Scholar
  104. 104.
    Magi-Galluzzi C, Tsusuki T, Elson P, Simmerman K, LaFargue C, Esgueva R, et al. TMPRSS2-ERG gene fusion prevalence and class are significantly different in prostate cancer of Caucasian, African-American and Japanese patients. Prostate. 2011;71(5):489–97. doi: 10.1002/pros.21265.PubMedCrossRefGoogle Scholar
  105. 105.
    Marks LS, Andriole GL, Fitzpatrick JM, Schulman CC, Roehrborn CG. The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations. J Urol. 2006;176(3):868–74. doi: 10.1016/j.juro.2006.04.024.PubMedCrossRefGoogle Scholar
  106. 106.
    Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SM, et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology. 2007;69(3):532–5. doi: 10.1016/j.urology.2006.12.014.PubMedCrossRefGoogle Scholar
  107. 107.
    McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. Reporting recommendations for tumor marker prognostic studies. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(36):9067–72. doi: 10.1200/JCO.2004.01.0454.CrossRefGoogle Scholar
  108. 108.
    Melling N, Thomsen E, Tsourlakis MC, Kluth M, Hube-Magg C, Minner S, et al. Overexpression of enhancer of zeste homolog 2 (EZH2) characterizes an aggressive subset of prostate cancers and predicts patient prognosis independently from pre- and postoperatively assessed clinicopathological parameters. Carcinogenesis. 2015;36(11):1333–40. doi: 10.1093/carcin/bgv137.PubMedCrossRefGoogle Scholar
  109. 109.
    Mikolajczyk SD, Catalona WJ, Evans CL, Linton HJ, Millar LS, Marker KM, et al. Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. Clin Chem. 2004;50(6):1017–25. doi: 10.1373/clinchem.2003.026823.PubMedCrossRefGoogle Scholar
  110. 110.
    Mikolajczyk SD, Grauer LS, Millar LS, Hill TM, Kumar A, Rittenhouse HG, et al. A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology. 1997;50(5):710–4. doi: 10.1016/S0090-4295(97)00449-4.PubMedCrossRefGoogle Scholar
  111. 111.
    Mikolajczyk SD, Millar LS, Wang TJ, Rittenhouse HG, Marks LS, Song W, et al. A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. Cancer Res. 2000;60(3):756–9.PubMedGoogle Scholar
  112. 112.
    Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol. 2010;2010:617421. doi: 10.1155/2010/617421.PubMedCrossRefGoogle Scholar
  113. 113.
    Minner S, Enodien M, Sirma H, Luebke AM, Krohn A, Mayer PS, et al. ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of anti-hormonal therapy. Clin Cancer Res. 2011;17(18):5878–88.PubMedCrossRefGoogle Scholar
  114. 114.
    Morgan TO, Jacobsen SJ, McCarthy WF, Jacobson DJ, McLeod DG, Moul JW. Age-specific reference ranges for prostate-specific antigen in black men. N Engl J Med. 1996;335(5):304–10. doi: 10.1056/NEJM199608013350502.PubMedCrossRefGoogle Scholar
  115. 115.
    Nakanishi H, Groskopf J, Fritsche HA, Bhadkamkar V, Blase A, Kumar SV, et al. PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol. 2008;179(5):1804–9. doi: 10.1016/j.juro.2008.01.013; discussion 9–10.PubMedCrossRefGoogle Scholar
  116. 116.
    Nam RK, Diamandis EP, Toi A, Trachtenberg J, Magklara A, Scorilas A, et al. Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen. J Clin Oncol Off J Am Soc Clin Oncol. 2000;18(5):1036–42.Google Scholar
  117. 117.
    Nam RK, Sugar L, Yang W, Srivastava S, Klotz LH, Yang LY, et al. Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br J Cancer. 2007;97(12):1690–5. doi: 10.1038/sj.bjc.6604054.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Nordstrom T, Vickers A, Assel M, Lilja H, Gronberg H, Eklund M. Comparison between the four-kallikrein panel and prostate health index for predicting prostate cancer. Eur Urol. 2015;68(1):139–46. doi: 10.1016/j.eururo.2014.08.010.PubMedCrossRefGoogle Scholar
  119. 119.
    Ohori M, Dunn JK, Scardino PT. Is prostate-specific antigen density more useful than prostate-specific antigen levels in the diagnosis of prostate cancer? Urology. 1995;46(5):666–71. doi: 10.1016/S0090-4295(99)80298-2.PubMedCrossRefGoogle Scholar
  120. 120.
    Papagiannakopoulos T, Shapiro A, Kosik KS. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008;68(19):8164–72. doi: 10.1158/0008-5472.CAN-08-1305.PubMedCrossRefGoogle Scholar
  121. 121.
    Parekh DJ, Punnen S, Sjoberg DD, Asroff SW, Bailen JL, Cochran JS, et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 2015;68(3):464–70. doi: 10.1016/j.eururo.2014.10.021.PubMedCrossRefGoogle Scholar
  122. 122.
    Park K, Tomlins SA, Mudaliar KM, Chiu YL, Esgueva R, Mehra R, et al. Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia. 2010;12(7):590–8.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Partin AW, Van Neste L, Klein EA, Marks LS, Gee JR, Troyer DA, et al. Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol. 2014;192(4):1081–7. doi: 10.1016/j.juro.2014.04.013.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Pettersson A, Graff RE, Bauer SR, Pitt MJ, Lis RT, Stack EC, et al. The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis. Cancer Epidemiol Biomarkers Prev Publ Am Assoc Cancer Res cosponsored by the Am Soc Prev Oncol. 2012;21(9):1497–509. doi: 10.1158/1055-9965.EPI-12-0042.CrossRefGoogle Scholar
  125. 125.
    Ploussard G, Durand X, Xylinas E, Moutereau S, Radulescu C, Forgue A, et al. Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer patients for active surveillance. Eur Urol. 2011;59(3):422–9. doi: 10.1016/j.eururo.2010.11.044.PubMedCrossRefGoogle Scholar
  126. 126.
    Priulla M, Calastretti A, Bruno P, Azzariti A, Paradiso A, Canti G, et al. Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. Prostate. 2007;67(7):782–9. doi: 10.1002/pros.20566.PubMedCrossRefGoogle Scholar
  127. 127.
    Qiu SD, Young CY, Bilhartz DL, Prescott JL, Farrow GM, He WW, et al. In situ hybridization of prostate-specific antigen mRNA in human prostate. J Urol. 1990;144(6):1550–6.PubMedGoogle Scholar
  128. 128.
    Recker F, Kwiatkowski MK, Piironen T, Pettersson K, Lummen G, Wernli M, et al. The importance of human glandular kallikrein and its correlation with different prostate specific antigen serum forms in the detection of prostate carcinoma. Cancer. 1998;83(12):2540–7.PubMedCrossRefGoogle Scholar
  129. 129.
    Rescigno P, Lorente D, Bianchini D, Ferraldeschi R, Kolinsky MP, Sideris S, et al. Prostate-specific antigen decline after 4 weeks of treatment with abiraterone acetate and overall survival in patients with metastatic castration-resistant prostate cancer. Eur Urol. 2016.Google Scholar
  130. 130.
    Ribas J, Ni X, Haffner M, Wentzel EA, Salmasi AH, Chowdhury WH, et al. miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res. 2009;69(18):7165–9. doi: 10.1158/0008-5472.CAN-09-1448.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Rommel FM, Agusta VE, Breslin JA, Huffnagle HW, Pohl CE, Sieber PR, et al. The use of prostate specific antigen and prostate specific antigen density in the diagnosis of prostate cancer in a community based urology practice. J Urol. 1994;151(1):88–93.PubMedGoogle Scholar
  132. 132.
    Scalzo DA, Kallakury BV, Gaddipati RV, Sheehan CE, Keys HM, Savage D, et al. Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas. Am J Clin Pathol. 1998;109(2):163–8.PubMedCrossRefGoogle Scholar
  133. 133.
    Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D, et al. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 2009;10(3):233–9. doi: 10.1016/S1470-2045(08)70340-1.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182(3):311–22. doi:10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9.PubMedCrossRefGoogle Scholar
  135. 135.
    Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014;384(9959):2027–35.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Schroder F, Kattan MW. The comparability of models for predicting the risk of a positive prostate biopsy with prostate-specific antigen alone: a systematic review. Eur Urol. 2008;54(2):274–90. doi: 10.1016/j.eururo.2008.05.022.PubMedCrossRefGoogle Scholar
  137. 137.
    Shen MM, Abate-Shen C. Pten inactivation and the emergence of androgen-independent prostate cancer. Cancer Res. 2007;67(14):6535–8. doi: 10.1158/0008-5472.CAN-07-1271.PubMedCrossRefGoogle Scholar
  138. 138.
    Sommariva S, Tarricone R, Lazzeri M, Ricciardi W, Montorsi F. Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;69(1):107–15. doi: 10.1016/j.eururo.2014.11.038.PubMedCrossRefGoogle Scholar
  139. 139.
    Stewart GD, Van Neste L, Delvenne P, Delree P, Delga A, McNeill SA, et al. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol. 2013;189(3):1110–6. doi: 10.1016/j.juro.2012.08.219.PubMedCrossRefGoogle Scholar
  140. 140.
    Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, et al. An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 2007;282(4):2135–43. doi: 10.1074/jbc.M608939200.PubMedCrossRefGoogle Scholar
  141. 141.
    Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988;102(4):639–55.PubMedGoogle Scholar
  142. 142.
    Tallon L, Luangphakdy D, Ruffion A, Colombel M, Devonec M, Champetier D, et al. Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness. Int J Mol Sci. 2014;15(8):13299–316. doi: 10.3390/ijms150813299.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS, et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2006;98(8):529–34. doi: 10.1093/jnci/djj131.PubMedCrossRefGoogle Scholar
  144. 144.
    Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA. 2005;294(1):66–70. doi: 10.1001/jama.294.1.66.PubMedCrossRefGoogle Scholar
  145. 145.
    Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004;350(22):2239–46. doi: 10.1056/NEJMoa031918.PubMedCrossRefGoogle Scholar
  146. 146.
    Tomlins SA, Day JR, Lonigro RJ, Hovelson DH, Siddiqui J, Kunju LP, et al. Urine TMPRSS2:ERG plus PCA3 for individualized prostate cancer risk assessment. Eur Urol. 2015. doi: 10.1016/j.eururo.2015.04.039.PubMedCentralGoogle Scholar
  147. 147.
    Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE, et al. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 2006;66(7):3396–400. doi: 10.1158/0008-5472.CAN-06-0168.PubMedCrossRefGoogle Scholar
  148. 148.
    Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644–8. doi: 10.1126/science.1117679.PubMedCrossRefGoogle Scholar
  149. 149.
    Ulmert D, Becker C, Nilsson JA, Piironen T, Bjork T, Hugosson J, et al. Reproducibility and accuracy of measurements of free and total prostate-specific antigen in serum vs plasma after long-term storage at −20 degrees C. Clin Chem. 2006;52(2):235–9. doi: 10.1373/clinchem.2005.050641.PubMedCrossRefGoogle Scholar
  150. 150.
    Ulmert D, Cronin AM, Bjork T, O’Brien MF, Scardino PT, Eastham JA, et al. Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: a case–control study. BMC Med. 2008;6:6. doi: 10.1186/1741-7015-6-6.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Umbas R, Isaacs WB, Bringuier PP, Xue Y, Debruyne FM, Schalken JA. Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer. Int J Cancer. 1997;74(4):374–7.PubMedCrossRefGoogle Scholar
  152. 152.
    Umbas R, Schalken JA, Aalders TW, Carter BS, Karthaus HF, Schaafsma HE, et al. Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. Cancer Res. 1992;52(18):5104–9.PubMedGoogle Scholar
  153. 153.
    Uzoh CC, Perks CM, Bahl A, Holly JM, Sugiono M, Persad RA. PTEN-mediated pathways and their association with treatment-resistant prostate cancer. BJU Int. 2009;104(4):556–61. doi: 10.1111/j.1464-410X.2009.08411.x.PubMedCrossRefGoogle Scholar
  154. 154.
    van den Bergh RC, Roobol MJ, Wolters T, van Leeuwen PJ, Schroder FH. The Prostate Cancer Prevention Trial and European Randomized Study of Screening for Prostate Cancer risk calculators indicating a positive prostate biopsy: a comparison. BJU Int. 2008;102(9):1068–73. doi: 10.1111/j.1464-410X.2008.07940.x.PubMedCrossRefGoogle Scholar
  155. 155.
    van Gils MP, Hessels D, de Kaa CA H-v, Witjes JA, Jansen CF, Mulders PF, et al. Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate. 2008;68(11):1215–22. doi: 10.1002/pros.20781.PubMedCrossRefGoogle Scholar
  156. 156.
    van Neste L, Hendriks RJ, Dijkstra S, Trooskens G, Cornel EB, Jannink SA, et al. Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Eur Urol. 2016. In press.Google Scholar
  157. 157.
    Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9. doi: 10.1038/nature01075.PubMedCrossRefGoogle Scholar
  158. 158.
    Vedder MM, de Bekker-Grob EW, Lilja HG, Vickers AJ, van Leenders GJ, Steyerberg EW, et al. The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC risk calculator for prostate cancer in prescreened men. Eur Urol. 2014;66(6):1109–15. doi: 10.1016/j.eururo.2014.08.011.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Vickers AJ, Cronin AM, Aus G, Pihl CG, Becker C, Pettersson K, et al. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Goteborg, Sweden. BMC Med. 2008;6:19. doi: 10.1186/1741-7015-6-19.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Vickers AJ, Savage C, O’Brien MF, Lilja H. Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(3):398–403. doi: 10.1200/JCO.2008.18.1685.CrossRefGoogle Scholar
  161. 161.
    Waltering KK, Porkka KP, Jalava SE, Urbanucci A, Kohonen PJ, Latonen LM, et al. Androgen regulation of micro-RNAs in prostate cancer. Prostate. 2011;71(6):604–14. doi: 10.1002/pros.21276.PubMedCrossRefGoogle Scholar
  162. 162.
    Wang J, Cai Y, Ren C, Ittmann M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res. 2006;66(17):8347–51. doi: 10.1158/0008-5472.CAN-06-1966.PubMedCrossRefGoogle Scholar
  163. 163.
    Wei JT, Feng Z, Partin AW, Brown E, Thompson I, Sokoll L, et al. Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(36):4066–72. doi: 10.1200/JCO.2013.52.8505.CrossRefGoogle Scholar
  164. 164.
    Whitman EJ, Groskopf J, Ali A, Chen Y, Blase A, Furusato B, et al. PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol. 2008;180(5):1975–8. doi: 10.1016/j.juro.2008.07.060; discussion 8–9.PubMedCrossRefGoogle Scholar
  165. 165.
    Woodrum DL, Brawer MK, Partin AW, Catalona WJ, Southwick PC. Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. J Urol. 1998;159(1):5–12.PubMedCrossRefGoogle Scholar
  166. 166.
    Wu Z, McRoberts KS, Theodorescu D. The role of PTEN in prostate cancer cell tropism to the bone micro-environment. Carcinogenesis. 2007;28(7):1393–400. doi: 10.1093/carcin/bgm050.PubMedCrossRefGoogle Scholar
  167. 167.
    Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev. 2001;22(2):184–204. doi: 10.1210/edrv.22.2.0424.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • S. Dijkstra
    • 1
  • R. J. Hendriks
    • 1
  • G. H. J. M. Leyten
    • 1
  • P. F. A. Mulders
    • 1
  • J. A. Schalken
    • 1
  1. 1.Radboud University Medical Center, Department of UrologyNijmegenThe Netherlands

Personalised recommendations