• 1
    Yousef GM, Luo LY, Diamandis EP. Identification of novel human kallikrein-like genes on chromosome 19q13.3-q13.4. Anticancer Res 1999; 19: 28432852
  • 2
    Clements J, Hooper J, Dong Y, Harvey T. The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. Biol Chem 2001; 382: 514
  • 3
    Kumar A, Mikolajczyk SD, Goel AS, Millar LS, Saedi MS. Expression of pro form of prostate-specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2. Cancer Res 1997; 57: 31113114
  • 4
    Lovgren J, Rajakoski K, Karp M. Lundwall Å, Lilja H. Activation of the zymogen form of prostate-specific antigen by human glandular kallikrein 2. Biochem Biophys Res Commun 1997; 238: 549555
  • 5
    Takayama TK, Fujikawa K, Davie EW. Characterization of the precursor of prostate-specific antigen. Activation by trypsin and by human glandular kallikrein. J Biol Chem 1997; 272: 2158221588
  • 6
    Takayama TK, McMullen BA, Nelson PS, Matsumura M, Fujikawa K. Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. Biochemistry 2001; 40: 1534115348
  • 7
    Lilja H, Oldbring J, Rannevik G, Laurell CB. Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. J Clin Invest 1987; 80: 281285
  • 8
    Stephan C, Jung K, Lein M, Diamandis EP. PSA and other tissue kallikreins for prostate cancer detection. Eur J Cancer 2007; 43: 19181926
  • 9
    Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317: 909916
  • 10
    Thompson IM, Pauler DK, Goodman PJ 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: 22392246
  • 11
    Lilja H, Christensson A, Dahlen U et al. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. Clin Chem 1991; 37: 16181625
  • 12
    Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res 1991; 51: 222226
  • 13
    Mikolajczyk SD, Marks LS, Partin AW, Rittenhouse HG. Free prostate-specific antigen in serum is becoming more complex. Urology 2002; 59: 797802
  • 14
    Mikolajczyk SD, Millar LS, Marker KM et al. Seminal plasma contains ‘BPSA,’ a molecular form of prostate-specific antigen that is associated with benign prostatic hyperplasia. Prostate 2000; 45: 271276
  • 15
    Mikolajczyk SD, Millar LS, Wang TJ et al. ‘BPSA,’ a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia. Urology 2000; 55: 4145
  • 16
    Mikolajczyk SD, Millar LS, Wang TJ 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: 756759
  • 17
    Mikolajczyk SD, Grauer LS, Millar LS et al. A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology 1997; 50: 710714
  • 18
    Sokoll LJ, Chan DW, Mikolajczyk SD et al. Proenzyme PSA for the early detection of prostate cancer in the 2.5–4.0 ng/ml total PSA range: preliminary analysis. Urology 2003; 61: 274276
  • 19
    Khan MA, Partin AW, Rittenhouse HG et al. Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml. J Urol 2003; 170: 723726
  • 20
    Catalona WJ, Bartsch G, Rittenhouse HG 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: 21812185
  • 21
    Catalona WJ, Bartsch G, Rittenhouse HG et al. Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen. J Urol 2004; 171: 22392244
  • 22
    Catalona WJ, Partin AW, Slawin KM 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: 15421547
  • 23
    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: 512
  • 24
    Mikolajczyk SD, Catalona WJ, Evans CL et al. Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. Clin Chem 2004; 50: 10171025
  • 25
    Khan MA, Sokoll LJ, Chan DW et al. Clinical utility of proPSA and ‘benign’ PSA when percent free PSA is less than 15%. Urology 2004; 64: 11601164
  • 26
    de Vries SH, Raaijmakers R, Blijenberg BG, Mikolajczyk SD, Rittenhouse HG, Schroder FH. Additional use of [-2] precursor prostate-specific antigen and ‘benign’ PSA at diagnosis in screen-detected prostate cancer. Urology 2005; 65: 926930
  • 27
    Bangma CH, Wildhagen MF, Yurdakul G, Schroder FH, Blijenberg BG. The value of (-7, -5)pro-prostate-specific antigen and human kallikrein-2 as serum markers for grading prostate cancer. BJU Int 2004; 93: 720724
  • 28
    Lein M, Semjonow A, Graefen M et al. A multicenter clinical trial on the use of (-5, -7) pro prostate specific antigen. J Urol 2005; 174: 21502153
  • 29
    Stephan C, Meyer HA, Kwiatkowski M et al. A (-5, -7) proPSA based artificial neural network to detect prostate cancer. Eur Urol 2006; 50: 10141020
  • 30
    Miyakubo M, Ito K, Yamamoto T, Takechi H, Ohi M, Suzuki K. Proprostate-specific antigen: its usefulness in the era of multiple-core prostate biopsy. Int J Urol 2009; 16: 561565
  • 31
    Stephan C, Meyer HA, Paul EM et al. Serum (-5, -7) proPSA for distinguishing stage and grade of prostate cancer. Anticancer Res 2007; 27: 18331836
  • 32
    Mikolajczyk SD, Marker KM, Millar LS et al. A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res 2001; 61: 69586963
  • 33
    Sokoll LJ, Wang Y, Feng Z et al. [-2]proenzyme prostate specific antigen for prostate cancer detection: a national cancer institute early detection research network validation study. J Urol 2008; 180: 539543
  • 34
    Sokoll LJ, Sanda MG, Feng Z et al. A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [-2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol Biomarkers Prev 2010 19: 11931200
  • 35
    Stephan C, Kahrs AM, Cammann H et al. A [-2]proPSA-based artificial neural network significantly improves differentiation between prostate cancer and benign prostatic diseases. Prostate 2009; 69: 198207
  • 36
    Rhodes T, Jacobson DJ, McGree ME et al. Longitudinal changes of benign prostate-specific antigen and [-2]proprostate-specific antigen in seven years in a community-based sample of men. Urology 2012; 79: 655661
  • 37
    Rhodes T, Jacobson DJ, McGree ME et al. Distribution and associations of [-2]proenzyme-prostate specific antigen in community dwelling black and white men. J Urol 2012; 187: 9296
  • 38
    Le BV, Griffin CR, Loeb S et al. [-2]Proenzyme prostate specific antigen is more accurate than total and free prostate specific antigen in differentiating prostate cancer from benign disease in a prospective prostate cancer screening study. J Urol 2010; 183: 13551359
  • 39
    Jansen FH, van Schaik RH, Kurstjens J et al. Prostate-specific antigen (PSA) isoform p2PSA in combination with total PSA and free PSA improves diagnostic accuracy in prostate cancer detection. Eur Urol 2010; 57: 921927
  • 40
    Catalona WJ, Partin AW, Sanda MG 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: 16501655
  • 41
    Guazzoni G, Nava L, Lazzeri M 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: 214222
  • 42
    Guazzoni G, Lazzeri M, Nava L 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. Eur Urol 2012; 61: 455466
  • 43
    Draisma G, Boer R, Otto SJ et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst 2003; 95: 868878
  • 44
    Makarov DV, Isharwal S, Sokoll LJ et al. Pro-prostate-specific antigen measurements in serum and tissue are associated with treatment necessity among men enrolled in expectant management for prostate cancer. Clin Cancer Res 2009; 15: 73167321
  • 45
    Isharwal S, Makarov DV, Sokoll LJ et al. ProPSA and diagnostic biopsy tissue DNA content combination improves accuracy to predict need for prostate cancer treatment among men enrolled in an active surveillance program. Urology 2011; 77: 763. e1–6
  • 46
    Nichol MB, Wu J, An JJ et al. Budget impact analysis of a new prostate cancer risk index for prostate cancer detection. Prostate Cancer Prostatic Dis 2011; 14: 253261
  • 47
    Nichol MB, Wu J, Huang J, Denham D, Frencher SK, Jacobsen SJ. Cost-effectiveness of prostate health index for prostate cancer detection. BJU Int 2011. [Epub ahead of print]. DOI: 10.1111/j.1464-410X.2011.10751.x
  • 48
    Heijnsdijk E, Huang J, Denham D, De Koning H. The cost-effectiveness of prostate cancer detection using Beckman Coulter Prostate Health Index. 2012. Proceeding of the 27th Annual European Association of Urology Congress in Paris, France. Available at: Accessed May 2012
  • 49
    Vickers AJ, Cronin AM, Aus G 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
  • 50
    Vickers A, Cronin A, Roobol M et al. Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication. J Clin Oncol 2010; 28: 24932498
  • 51
    Sottile A, Ortega C, Berruti A et al. A pilot study evaluating serum pro-prostate-specific antigen in patients with rising PSA following radical prostatectomy. Oncol Lett 2012 3: 819824