Biomarkers for Prostate Cancer

  • Gisele H. J. M. Leyten
  • Peter F. A. Mulders
  • Jack A. Schalken


In the last decade, revolutionary advancements in molecular profiling technologies have been made resulting in new diagnostic algorithms. These advances have marked the beginning of a new era for modern medicine: individualized medicine. Biomarkers are important tools in individualized medicine, to accurately predict the biological behavior and therapy response for well-stratified/homogeneous groups of patients. This chapter will focus on established biomarkers for prostate cancer and promising novel biomarkers, arranged by 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 tumor marker studies.


Prostate Cancer Radical Prostatectomy Digital Rectal Examination Aggressive Prostate Cancer 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.


  1. Aaltomaa S, Lipponen P, Vesalainen S et al (1997) Value of Ki-67 immunolabelling as a prognostic factor in prostate cancer. Eur Urol 32:410–415PubMedGoogle Scholar
  2. Anai S, Goodison S, Shiverick K et al (2006) Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. Hum Gene Ther 17:975–984PubMedGoogle Scholar
  3. Ang JE, Olmos D, de Bono JS (2009) CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer. Br J Cancer 100:671–675PubMedGoogle Scholar
  4. Ankerst DP, Groskopf J, Day JR et al (2008) Predicting prostate cancer risk through incorporation of prostate cancer gene 3. J Urol 180:1303–1308; discussion 8PubMedGoogle Scholar
  5. Attard G, Clark J, Ambroisine L et al (2008) Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer. Br J Cancer 99:314–320PubMedGoogle Scholar
  6. Auprich M, Haese A, Walz J et al (2010) External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome. Eur Urol 58:727–732PubMedGoogle Scholar
  7. Auprich M, Chun FK, Ward JF et al (2011) Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging. Eur Urol 59:96–105PubMedGoogle Scholar
  8. Barry MJ (2001) Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. N Engl J Med 344:1373–1377PubMedGoogle Scholar
  9. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedGoogle Scholar
  10. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233PubMedGoogle Scholar
  11. Becker C, Piironen T, Pettersson K et al (2000) 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 55:694–699PubMedGoogle Scholar
  12. Bedolla R, Prihoda TJ, Kreisberg JI et al (2007) Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression and Akt activation. Clin Cancer Res 13:3860–3867PubMedGoogle Scholar
  13. Benson MC, Whang IS, Pantuck A et al (1992) Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. J Urol 147:815–816PubMedGoogle Scholar
  14. Bettencourt MC, Bauer JJ, Sesterhenn IA et al (1996) Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol 156:1064–1068PubMedGoogle Scholar
  15. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95Google Scholar
  16. Birchmeier W, Behrens J (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1198:11–26PubMedGoogle Scholar
  17. Bonci D, Coppola V, Musumeci M et al (2008) The miR-15a-miR-16–1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14:1271–1277PubMedGoogle Scholar
  18. Borer JG, Sherman J, Solomon MC et al (1998) Age specific prostate specific antigen reference ranges: population specific. J Urol 159:444–448PubMedGoogle Scholar
  19. Borre M, Bentzen SM, Nerstrom B et al (1998) Tumor cell proliferation and survival in patients with prostate cancer followed expectantly. J Urol 159:1609–1614PubMedGoogle Scholar
  20. Bossuyt PM, Reitsma JB, Bruns DE et al (2003) The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem 49:7–18PubMedGoogle Scholar
  21. Bradford TJ, Tomlins SA, Wang X et al (2006) Molecular markers of prostate cancer. Urol Oncol 24:538–551PubMedGoogle Scholar
  22. Brawer MK, Aramburu EA, Chen GL et al (1993) 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 150:369–373PubMedGoogle Scholar
  23. Breuer RH, Snijders PJ, Smit EF et al (2004) Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis. Neoplasia 6:736–743PubMedGoogle Scholar
  24. Bubendorf L, Sauter G, Moch H et al (1996) Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol 178:437–441PubMedGoogle Scholar
  25. Bussemakers MJ, van Bokhoven A, Verhaegh GW et al (1999) DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 59:5975–5979PubMedGoogle Scholar
  26. Calin GA, Liu CG, Sevignani C et al (2004) MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 101:11755–11760PubMedGoogle Scholar
  27. Cao Q, Yu J, Dhanasekaran SM et al (2008) Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 27:7274–7284PubMedGoogle Scholar
  28. Catalona WJ, Partin AW, Slawin KM et al (1998) 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 279:1542–1547PubMedGoogle Scholar
  29. Catalona WJ, Bartsch G, Rittenhouse HG et al (2003) 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 170:2181–2185PubMedGoogle Scholar
  30. Cattoretti G, Becker MH, Key G et al (1992) 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 168:357–363PubMedGoogle Scholar
  31. Chen K, Rajewsky N (2007) The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8:93–103PubMedGoogle Scholar
  32. Chen H, Tu SW, Hsieh JT (2005) Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J Biol Chem 280:22437–22444PubMedGoogle Scholar
  33. Chun FK, de la Taille A, van Poppel H et al (2009) Prostate cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram. Eur Urol 56:659–667PubMedGoogle Scholar
  34. Cohen SJ, Punt CJ, Iannotti N et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26:3213–3221PubMedGoogle Scholar
  35. Cohen SJ, Punt CJ, Iannotti N et al (2009) Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol 20:1223–1229PubMedGoogle Scholar
  36. Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791PubMedGoogle Scholar
  37. Cristofanilli M, Hayes DF, Budd GT et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430PubMedGoogle Scholar
  38. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714PubMedGoogle Scholar
  39. D’Amico AV, Roehrborn CG (2007) Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol 8:21–25PubMedGoogle Scholar
  40. Danila DC, Heller G, Gignac GA et al (2007) Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 13:7053–7058PubMedGoogle Scholar
  41. de Bono JS, Scher HI, Montgomery RB et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14:6302–6309PubMedGoogle Scholar
  42. de la Taille A, Irani J, Graefen M et al (2011) Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 185:2119–2125PubMedGoogle Scholar
  43. Deininger M, Buchdunger E, Druker BJ (2005) The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 105:2640–2653PubMedGoogle Scholar
  44. Demichelis F, Fall K, Perner S et al (2007) TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 26:4596–4599PubMedGoogle Scholar
  45. Deras IL, Aubin SM, Blase A et al (2008) PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 179:1587–1592PubMedGoogle Scholar
  46. di Sant’Agnese PA, de Mesy Jensen KL (1987) Neuroendocrine differentiation in prostatic carcinoma. Hum Pathol 18:849–856PubMedGoogle Scholar
  47. Duffy MJ (2002) Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers. Biochem Soc Trans 30:207–210PubMedGoogle Scholar
  48. Efstathiou JA, Chen MH, Catalona WJ et al (2006) Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality. Urology 68:342–347PubMedGoogle Scholar
  49. FitzGerald LM, Agalliu I, Johnson K et al (2008) Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer 8:230PubMedGoogle Scholar
  50. Fowler JE Jr, Bigler SA, Kilambi NK et al (1999) Relationships between prostate-specific antigen and prostate volume in black and white men with benign prostate biopsies. Urology 53:1175–1178PubMedGoogle Scholar
  51. Galardi S, Mercatelli N, Giorda E et al (2007) miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem 282:23716–23724PubMedGoogle Scholar
  52. Gopalan A, Leversha MA, Satagopan JM et al (2009) TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res 69:1400–1406PubMedGoogle Scholar
  53. Groskopf J, Aubin SM, Deras IL et al (2006) APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 52:1089–1095PubMedGoogle Scholar
  54. Guo H, Ingolia NT, Weissman JS et al (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835–840PubMedGoogle Scholar
  55. Gutman AB, Gutman EB (1938) An “acid” phosphatase occurring in the serum of patients with metastasizing carcinoma of the prostate gland. J Clin Invest 17:473–478PubMedGoogle Scholar
  56. Haese A, Graefen M, Steuber T et al (2001) 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 49:101–109PubMedGoogle Scholar
  57. Haese A, de la Taille A, van Poppel H et al (2008) Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 54:1081–1088PubMedGoogle Scholar
  58. Han B, Mehra R, Dhanasekaran SM et al (2008) A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer. Cancer Res 68:7629–7637PubMedGoogle Scholar
  59. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531PubMedGoogle Scholar
  60. Herrala AM, Porvari KS, Kyllonen AP et al (2001) 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 92:2975–2984PubMedGoogle Scholar
  61. Hessels D, Klein Gunnewiek JM, van Oort I et al (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44:8–15; discussion 15–16PubMedGoogle Scholar
  62. Hessels D, Smit FP, Verhaegh GW et al (2007) Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res 13:5103–5108PubMedGoogle Scholar
  63. Hessels D, van Gils MP, van Hooij O et al (2010) Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate 70:10–16PubMedGoogle Scholar
  64. Huang H, Cheville JC, Pan Y et al (2001) PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem 276:38830–38836PubMedGoogle Scholar
  65. Ioannidis JP, Castaldi P, Evangelou E (2010) A compendium of genome-wide associations for cancer: critical synopsis and reappraisal. J Natl Cancer Inst 102:846–858PubMedGoogle Scholar
  66. Josson S, Sung SY, Lao K et al (2008) Radiation modulation of microRNA in prostate cancer cell lines. Prostate 68:1599–1606PubMedGoogle Scholar
  67. Karazanashvili G, Abrahamsson PA (2003) Prostate specific antigen and human glandular kallikrein 2 in early detection of prostate cancer. J Urol 169:445–457PubMedGoogle Scholar
  68. Kleer CG, Cao Q, Varambally S et al (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100:11606–11611PubMedGoogle Scholar
  69. Koyanagi M, Baguet A, Martens J et al (2005) EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells. J Biol Chem 280:31470–31477PubMedGoogle Scholar
  70. Kumaresan K, Kakkar N, Verma A et al (2010) Diagnostic utility of alpha-methylacyl CoA racemase (P504S) & HMWCK in morphologically difficult prostate cancer. Diagn Pathol 5:83PubMedGoogle Scholar
  71. Laxman B, Tomlins SA, Mehra R et al (2006) Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 8:885–888PubMedGoogle Scholar
  72. Li J, Yen C, Liaw D et al (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947PubMedGoogle Scholar
  73. Lilja H (1985) A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 76:1899–1903PubMedGoogle Scholar
  74. Lilja H, Ulmert D, Bjork T et al (2007) 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 25:431–436PubMedGoogle Scholar
  75. Lilja H, Ulmert D, Vickers AJ (2008) Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer 8:268–278PubMedGoogle Scholar
  76. Lin SL, Chiang A, Chang D et al (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14:417–424PubMedGoogle Scholar
  77. Linton HJ, Marks LS, Millar LS et al (2003) Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease. Clin Chem 49:253–259PubMedGoogle Scholar
  78. Lintula S, Stenman J, Bjartell A et al (2005) Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissue. Prostate 63:324–329PubMedGoogle Scholar
  79. Loeb S, Roehl KA, Antenor JA et al (2006) 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 67:316–320PubMedGoogle Scholar
  80. Lundwall A, Clauss A, Olsson AY (2006) Evolution of kallikrein-related peptidases in mammals and identification of a genetic locus encoding potential regulatory inhibitors. Biol Chem 387:243–249PubMedGoogle Scholar
  81. Magi-Galluzzi C, Tsusuki T, Elson P et al (2011) TMPRSS2-ERG gene fusion prevalence and class are significantly different in prostate cancer of Caucasian, African-American and Japanese patients. Prostate 71:489–497PubMedGoogle Scholar
  82. Marks LS, Andriole GL, Fitzpatrick JM et al (2006) The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations. J Urol 176:868–874PubMedGoogle Scholar
  83. Marks LS, Fradet Y, Deras IL et al (2007) PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 69:532–535PubMedGoogle Scholar
  84. McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072PubMedGoogle Scholar
  85. Mikolajczyk SD, Grauer LS, Millar LS et al (1997) A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology 50:710–714PubMedGoogle Scholar
  86. Mikolajczyk SD, Millar LS, Wang TJ et al (2000) A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. Cancer Res 60:756–759PubMedGoogle Scholar
  87. Mikolajczyk SD, Catalona WJ, Evans CL et al (2004) Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. Clin Chem 50:1017–1025PubMedGoogle Scholar
  88. Miller MC, Doyle GV, Terstappen LW (2010) Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010:617421PubMedGoogle Scholar
  89. Minner S, Enodien M, Sirma H et al (2011) ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of anti-hormonal therapy. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-11-1251
  90. Morgan TO, Jacobsen SJ, McCarthy WF et al (1996) Age-specific reference ranges for prostate-specific antigen in black men. N Engl J Med 335:304–310PubMedGoogle Scholar
  91. Nakanishi H, Groskopf J, Fritsche HA et al (2008) PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol 179:1804–1809; discussion 9–10PubMedGoogle Scholar
  92. Nam RK, Diamandis EP, Toi A et al (2000) Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen. J Clin Oncol 18:1036–1042PubMedGoogle Scholar
  93. Nam RK, Sugar L, Yang W et al (2007) Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br J Cancer 97:1690–1695PubMedGoogle Scholar
  94. Ohori M, Dunn JK, Scardino PT (1995) Is prostate-specific antigen density more useful than prostate-specific antigen levels in the diagnosis of prostate cancer? Urology 46:666–671PubMedGoogle Scholar
  95. Papagiannakopoulos T, Shapiro A, Kosik KS (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68:8164–8172PubMedGoogle Scholar
  96. Park K, Tomlins SA, Mudaliar KM et al (2010) Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia 12:590–598PubMedGoogle Scholar
  97. Ploussard G, Durand X, Xylinas E et al (2011) Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer patients for active surveillance. Eur Urol 59:422–429PubMedGoogle Scholar
  98. Priulla M, Calastretti A, Bruno P et al (2007) Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. Prostate 67:782–789PubMedGoogle Scholar
  99. Qiu SD, Young CY, Bilhartz DL et al (1990) In situ hybridization of prostate-specific antigen mRNA in human prostate. J Urol 144:1550–1556PubMedGoogle Scholar
  100. Recker F, Kwiatkowski MK, Piironen T et al (1998) The importance of human glandular kallikrein and its correlation with different prostate specific antigen serum forms in the detection of prostate carcinoma. Cancer 83:2540–2547PubMedGoogle Scholar
  101. Ribas J, Ni X, Haffner M et al (2009) miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res 69:7165–7169PubMedGoogle Scholar
  102. Rommel FM, Agusta VE, Breslin JA et al (1994) 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 151:88–93PubMedGoogle Scholar
  103. Saramaki OR, Harjula AE, Martikainen PM et al (2008) TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res 14:3395–3400PubMedGoogle Scholar
  104. Scalzo DA, Kallakury BV, Gaddipati RV et al (1998) Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas. Am J Clin Pathol 109:163–168PubMedGoogle Scholar
  105. Scher HI, Jia X, de Bono JS et al (2009) Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 10:233–239PubMedGoogle Scholar
  106. Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322PubMedGoogle Scholar
  107. Schroder F, Kattan MW (2008) The comparability of models for predicting the risk of a positive prostate biopsy with prostate-specific antigen alone: a systematic review. Eur Urol 54:274–290PubMedGoogle Scholar
  108. Shen MM, Abate-Shen C (2007) Pten inactivation and the emergence of androgen-independent prostate cancer. Cancer Res 67:6535–6538PubMedGoogle Scholar
  109. Sylvestre Y, De Guire V, Querido E et al (2007) An E2F/miR-20a autoregulatory feedback loop. J Biol Chem 282:2135–2143PubMedGoogle Scholar
  110. Takeichi M (1988) The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development 102:639–655PubMedGoogle Scholar
  111. Thompson IM, Pauler DK, Goodman PJ et al (2004) Prevalence of prostate cancer among men with a prostate-specific antigen level  <  or =4.0 ng per milliliter. N Engl J Med 350:2239–2246PubMedGoogle Scholar
  112. Thompson IM, Ankerst DP, Chi C et al (2005) Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 294:66–70PubMedGoogle Scholar
  113. Thompson IM, Ankerst DP, Chi C et al (2006) Assessing prostate cancer risk: results from the prostate cancer prevention trial. J Natl Cancer Inst 98:529–534PubMedGoogle Scholar
  114. Tomlins SA, Rhodes DR, Perner S et al (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310:644–648PubMedGoogle Scholar
  115. Tomlins SA, Mehra R, Rhodes DR et al (2006) TMPRSS2:ETV4 gene fusions define a third mole­cular subtype of prostate cancer. Cancer Res 66:3396–3400PubMedGoogle Scholar
  116. Tomlins SA, Aubin SM, Siddiqui J et al (2011) Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med 3:94ra72PubMedGoogle Scholar
  117. Tosoian JJ, Loeb S, Kettermann A et al (2010) Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program. J Urol 183:534–538PubMedGoogle Scholar
  118. Ulmert D, Becker C, Nilsson JA et al (2006) 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 52:235–239PubMedGoogle Scholar
  119. Ulmert D, Cronin AM, Bjork T et al (2008) 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 6:6PubMedGoogle Scholar
  120. Umbas R, Schalken JA, Aalders TW et al (1992) Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. Cancer Res 52:5104–5109PubMedGoogle Scholar
  121. Umbas R, Isaacs WB, Bringuier PP et al (1997) Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer. Int J Cancer 74:374–377PubMedGoogle Scholar
  122. Uzoh CC, Perks CM, Bahl A et al (2009) PTEN-mediated pathways and their association with treatment-resistant prostate cancer. BJU Int 104:556–561PubMedGoogle Scholar
  123. van den Bergh RC, Roobol MJ, Wolters T et al (2008) 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 102:1068–1073PubMedGoogle Scholar
  124. van Gils MP, Hessels D, Hulsbergen-van de Kaa CA et al (2008) Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate 68:1215–1222PubMedGoogle Scholar
  125. Varambally S, Dhanasekaran SM, Zhou M et al (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419:624–629PubMedGoogle Scholar
  126. Vickers AJ, Savage C, O’Brien MF et al (2009) Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol 27:398–403PubMedGoogle Scholar
  127. Waltering KK, Porkka KP, Jalava SE et al (2011) Androgen regulation of micro-RNAs in prostate cancer. Prostate 71:604–614PubMedGoogle Scholar
  128. Wang J, Cai Y, Ren C et al (2006) Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res 66:8347–8351PubMedGoogle Scholar
  129. Whitman EJ, Groskopf J, Ali A et al (2008) PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol 180:1975–1978; discussion 8–9PubMedGoogle Scholar
  130. Winnes M, Lissbrant E, Damber JE et al (2007) Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer. Oncol Rep 17:1033–1036PubMedGoogle Scholar
  131. Woodrum DL, Brawer MK, Partin AW et al (1998) Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. J Urol 159:5–12PubMedGoogle Scholar
  132. Wu Z, McRoberts KS, Theodorescu D (2007) The role of PTEN in prostate cancer cell tropism to the bone micro-environment. Carcinogenesis 28:1393–1400PubMedGoogle Scholar
  133. Yousef GM, Diamandis EP (2001) The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 22:184–204PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Gisele H. J. M. Leyten
    • 1
  • Peter F. A. Mulders
    • 1
  • Jack A. Schalken
    • 1
  1. 1.Department of UrologyRadboud University Nijmegen Medical CenterNijmegenNL

Personalised recommendations