Ces Urol 2008, 12(3):173-185 | DOI: 10.48095/cccu2008018

Tumor markers in prostate cancer diagnosis

Jiří Klečka1, Luboš Holubec3, Martin Pešta2, Milan Hora1, Ondřej Topolčan2, Viktor Eret1
1 Urologická klinika FN a LF UK, Plzeň
2 Centrální radioizotopová laboratoř LF UK, Plzeň
3 Radioterapeutické oddělení FN, Plzeň

Numerous attempts towards improving diagnostic, management and prognosis of the patients with prostate cancer by molecular staging have been fruitless so far. The reason is relatively low specifity of standard used tumor marker ? PSA (Prostatic Specific Antigen). No single molecular parameter is routinely analyzed in prostate cancer tissue. Powerful DNA array and proteomics methods allow the systematic analysis of virtually all genes of a cancer on the DNA, RNA, and protein level. In future, one of the major scientific challenges will be the validation of several potential biomarkers in large enough and clinically well characterized patient cohorts. As a promising gene based tumor marker seems to be detection of mRNA of prostate cancer specific DD3 gene (Diferential Display Code 3 gene).

Keywords: prostate cancer, markers, genes, prognosis, prediction

Received: July 15, 2008; Accepted: October 20, 2008; Published: June 1, 2008 

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References

  1. http://www.svod.cz/graph, software SVOD (Systém pro Vizualizaci Onkologických Dat, nyní ve verzi 6).
  2. Paulson DF, Moul JW,Walther PJ. Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long term results. J Urol 1990; 144(5): 1180-1184. Go to original source... Go to PubMed...
  3. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S,Théodore C,James ND,Turesson I,Rosenthal MA,Eisenberger MA. TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351(15): 1502-1512. Go to original source... Go to PubMed...
  4. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 2008; 26(2): 242-245. Go to original source... Go to PubMed...
  5. Klener P, Malbohan MI, Zima T. Nádorové markery. In Zima T, et al. Laboratorní diagnostika. Praha: Grada Publishing, a.s., 2007; 379-390.
  6. Ulmert H, Cronin AM, Bjork T, 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 Medicine 2008; 6: 1-8. Go to original source... Go to PubMed...
  7. Loeb S, Catalona WJ. What to do with an abnormal PSA test. The Oncologist 2008; 13: 299-305. Go to original source... Go to PubMed...
  8. Margreiter M, Stangelberger A, Valimberti E, Herwig R, Djavan B. Biomarkers for early prostate cancer detection. Minerva Urol Nefrol 2008; 60(1): 51-60.
  9. Vik V, Šácha P, Koukolík F, Konvalinka J, Pacík D, Zachoval R. Co nového víme o PSMA (prostatický specifický membránový antigen): z pohledu urologa. Urol List 2007; 5(4): 10-13.
  10. Lijovic M, Fabiani ME, Bader J, Frauman AG. Prostate cancer: are new prognostic markers on the horizon? Prostate cancer and Prostatic Disease 2000; 3: 62-65. Go to original source... Go to PubMed...
  11. Yoshida BA, Chekmareva MA, Wharam JF, et al. Prostate cancer metastasis-suppressor genes: a current perspective. In Vivo 1998; 12: 49-58.
  12. Tinzl M, Marberger M, Horvath S, Chypre C. DD3PCA3 RNA analysis in urine-a new perspective for detecting prostate cancer. Eur Urol 2004; 46(2): 182-186. Go to original source... Go to PubMed...
  13. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C. Chung LW, Hsieh JT, Tu SM, Campbell ML. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 1992; 52: 6940-6944.
  14. Cordon-Cardo C, Koff A, Drobnjak M, Capodieci P, Osman I, Miliard SS, Gaudin PB, Fazzari M, Zhang ZF, Massague J, Scher HI. Distinct altered patterns of p27KIPl gene expression in benign prostatic hyperplasia and prostatic carcinoma. J Nat Cancer Inst 1998; 90: 1284-1291. Go to original source... Go to PubMed...
  15. Cheville JC, Lloyd RV, Sebo TJ, Cheng L, Erickson L, Bostwick DG, Lohse CM,Wollan P. Expression of p27kip l in prostatic adenocarcinoma. Mod Pathol 1998; 11: 324-328.
  16. Tsihlias J, Kapusta LR, DeBoer G, Morava-Protzner I, Zbieranowski I, Bhattacharya N, Catzavelos GC, Klotz LH, Slingerland JM. Loss of cyclin-dependent kinase inhibitor p27Kip l is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res 1998; 58: 542-548.
  17. Vis AN, van Rhijn BW, Noordzij MA, Schroder FH, van der Kwast TH. Value of tissue markers p27(kipl), MIB-1, and CD44s for the preoperative prediction of tumour features in screen detected prostate cancer. J Pathol 2002; 197: 148-154. Go to original source... Go to PubMed...
  18. Shariff AH, Ather MH. Neuroendocrine differentiation in prostate cancer. Urology 2002; 68: 2-8. Go to original source... Go to PubMed...
  19. Casella R, Bubendorf L, Sauter G, Moch H, Mihatsch MJ, Gasser TC. Focal neuroendocrine differentiation lacks prognostic significance in prostate core needle biopsies. J Urol 1998; 160: 406-410. Go to original source... Go to PubMed...
  20. Bonkhoff H. Neuroendocrine differentiation in human prostate cancer. Morphogenesis, proliferation and androgen receptor status. Ann Oncol 2001; Suppl 2: 141-144. Go to original source... Go to PubMed...
  21. Bonkhoff H, Fixemer T. Neuroendocrine differentiation in prostate cancer: an unrecognized and therapy resistant phenotype. Pathologe 2005; 26: 453-460. Go to original source... Go to PubMed...
  22. Wright GL Jr, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, Troyer J, Konchuba A, Schellhammer PF, Moriarty R. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 1996; 48: 326-334. Go to original source... Go to PubMed...
  23. Karayi MK, Markham AF. Molecular biology of prostate cancer. Prostate Cancer Prostatic Dis. 2004; 7(1): 6-20. Go to original source... Go to PubMed...
  24. Marchal C, Redondo M, Padilla M, Caballero J, Rodrigo I, Garcia J, Quian J, Boswick DG. Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Histol Histopathol 2004; 19: 715-718.
  25. Reese DM, Smáli EJ, Magrane G, Waldman FM, Chew K, Sudilovsky D. HER2 protein expression and gene amplification in androgen-independent prostate cancer. Am J Clin Pathol 2001; 116: 234-239. Go to original source... Go to PubMed...
  26. Bubendorf L, Kononen J, Koivisto P, Schraml P, Moch H, Gasser TC, Willi N,Mihatsch MJ,Sauter G,Kallioniemi OP. Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res 1999; 59: 803-806.
  27. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Taň EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123-132. Go to original source... Go to PubMed...
  28. Di Lorenzo G, Tortora G, D'Armiento FP, De Rosa G, Staibano S, Autorino R, D'Armiento M, De Laurentiis M, De Placido S, Catalano G, Bianco AR, Ciardiello F. Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer. Clin Cancer Res 2002; 8: 3438-3444.
  29. Clements JA, Rohde P,Alien V, Hyland VJ, Samaratunga ML, Tilley WD, et al. Molecular detection of prostate cells in ejaculate and urethral washings in men with suspected prostate cancer. J Urol 1999; 161(4): 1337-1343. Go to original source... Go to PubMed...
  30. Ritter MA, Gilchrist KW, Voytovich M, Chappell RJ, Verhoven BM. The role of p53 in radiation therapy outcomes for favorable to intermediate risk prostate cancer. Int J Radiat Oncol Biol Phys 2002; 53: 574-580. Go to original source... Go to PubMed...
  31. Zellweger T, Ninck C, Bloch M, Mirlacher M, Koivisto PA, Helin HJ, Mihatsch MJ, Gasser TC, Bubendorf L. Expression patterns of potential therapeutic targets in prostate cancer. Int J Cancer 2005; 113: 619-628. Go to original source... Go to PubMed...
  32. Kaur P, Kallakury BS, Sheehan CE, Fisher HA, Kaufman RP Jr, Ross JS. Survivin and Bcl-2 expression in prostatic adenocarcinomas. Arch Pathol Lab Med 2004; 128: 33-39. Go to original source... Go to PubMed...
  33. Apakama I, Robinson MC, Walter NM, Charlton RG, Royds JA Fuller CE, Neal DE, Hamdy FC. Bcl-2 overexpres-sion combined with p53 protein accumulation correlates with hormone-refractory prostate cancer. Br J Cancer 1996; 74: 1258-1262. Go to original source... Go to PubMed...
  34. Colombel M,Symmans F,Gil S,OToole KM,Chopin D,Benson M,Olsson CA, Korsmeyer S, Buttyan R. Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 1993; 143: 390-399.
  35. Szostak MJ, Kaur P, Amin P, Jacobs SC. Kyprianou N. Apoptosis and bcl-2 expression in prostate cancer. significance in clinical outcome after brachytherapy. J Urol 2003; 165: 2126-2130. Go to original source... Go to PubMed...
  36. Masuda M, Takáno Y, Iki M,Asakura T, Hashiba T, Noguchi S, Hosaka M. Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis. Pathol Int 1998; 48: 41-46. Go to original source... Go to PubMed...
  37. Stattin P, Daraber JE, Karlberg L, Nordgren H, Bergh A. Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival. Urol Res 1996; 24: 257-264. Go to original source... Go to PubMed...
  38. Bubendorf L, Sauter G, Moch H, Jordán P, Blochlinger A, Gasser TC, Mihatsch MJ. Prognostic signiflcance of Bcl-2 in clinically localized prostate cancer. Am J Pathol 1996; 148: 1557-1565.
  39. Amirghofran Z, Monabati A, Gholijani N. Apoptosis in prostate cancer: bax correlation with stage. Int J Urol 2005; 12: 340-345. Go to original source... Go to PubMed...
  40. Iwakiri J, Granbois K, Wehner N, Graves HC, Stamey T. 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 1993; 149(4): 783-786. Go to original source... Go to PubMed...
  41. André F, Pusztai L. Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy. Nat Clin Pract Oncol 2006; 3: 621-632. Go to original source... Go to PubMed...
  42. Liu HL, Gandour-Edwards R, Lara PN Jr,White R, LaSalle JM. Detection of low levelHER2/neu gene amplification in prostate cancer by fluorescence in situ hybridization. Cancer J 2001; 7: 395-403. Go to original source...
  43. Montironi R, Mazzucchelli R, Barbisan F, Stramazzotti D, Santinelli A, Scarpelli M, Lopez Beltran A. HER2 expression and gene amplification in pT2a Gleason score 6 prostate cancer incidentally detected in cystoprostatectomies: comparison with clinically detected androgen-dependent and androgenindependent cancer. Hum Pathol 2006; 37: 1137-1144. Go to original source... Go to PubMed...
  44. Visakorpi T, Kallioniemi OP, Koivula T, Harvey J, Isola J. Expression of epidermal growth factor receptor and ERBB2 (HER-2/Neu) oncoprotein in prostatic carcinomas. Mod Pathol 1996; 5: 643-648.
  45. Schlomm T, Simon R, Huland H. Graefen M, Sauter G, Erbersdobler A. High EGFR expression is associated with poor prognosis in radically operated prostate cancer (submitted 2007).
  46. Edwards J, Traynor P, Munro AF, Pirret CF, Dunne B, Bart-lett JM. The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer. Clin Cancer Res 2006; 12: 123-130. Go to original source... Go to PubMed...
  47. Wilding G, Soulie P, Trump D, Das-Gupta A, Smali E. Results from a pilot phase I trial of gefitinib combined with docetaxel and estramustine in patients with hormone-refractory prostata cancer. Cancer 2006; 106: 1917-1924. Go to original source... Go to PubMed...
  48. Bauer JJ, Sesterhenn IA, Mostofi KF, McLeod DG, Srivastava S, Moul JW. P53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy. Clin Cancer Res 1995; 1: 1295-1300.
  49. Quinn DI, Henshall SM, Sutherland RL. Molecular markers of prostate cancer outcome. Eur J Cancer 2005; 41(6): 858-887. Go to original source... Go to PubMed...
  50. Kuczyk MA,Serth J,Bokemeyer C,Machtens S,MinssenA,BathkeW,Hartmann J, Jonas U. The prognostic value of p53 for long-term and recurrence-free survivalfollowingradicalprostatectomy.EurJCancer1998;34:679-686. Go to original source... Go to PubMed...
  51. Visakorpi T, Kallioniemi OP, Heikkinen A, Koivula T, Isola J. Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Nat Cancer Inst 1998; 84: 883-887. Go to original source... Go to PubMed...
  52. Henke RP, Kruger E, Ayhan N, Hubner D, Hammerer P, Huland H. Immunohistochemical detection of p53 protein in human prostatic cancer. J Urol 1994; 152: 1297-1301. Go to original source... Go to PubMed...
  53. Schlomm T, Iwers L, Kirstein P, Jessen B, Köllermann J, Minner S,Passow-Drolet A, Mirlacher M, Milde-Langosch K, Graefen M, Haese A, Steuber T, Simon R, Huland H, Sauter G, Erbersdobler A. Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol 2008; in press. Go to original source... Go to PubMed...
  54. Joly F, Henry-Amar M. Prognostic factors of localised, locally advanced or metastatic prostate cancer. Bull Cancer 2007; 94(Suppl 7): 35-43.
  55. Augustin H, Freibauer C, Bayer L, Lunglmayr G, Tschurlovich F, Kuber W, Pummer K. Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression. Eur Urol 2005; 150: 259-235.
  56. Scherr DS,Vaughan ED Jr.,Wei J,Chung M,Felsen D,All-bright R,Knudsen BS. BCL-2 and p53 expression in clinically localized prostate cancer predicts response to external beam radiotherapy. J Urol 1999; 162: 12-16. Go to original source... Go to PubMed...
  57. Incognito LS, Cazares LH, Schellhammer PF. Kuban DA, Van Dyk EO, Moriarty RP, Wright GL Jr, Somers KD. Overexpression of p53 in prostate carcinoma is associated with improved overall survival but not predictive of response to radiotherapy. Int J Oncol 2002; 17: 761-769.
  58. Rakozy C, Grignon DJ, Li Y, Gheiler E, Gururajanna B, Pontes JE, Sakr W, Wood DP Jr, Sarkar FH. P53 gene alterations in prostate cancer after radiation failure and their association with clinical outcome: a molecular and immuno-histochemical analysis. Pathol Res Pract 1999; 195: 129-135. Go to original source... Go to PubMed...
  59. Rakozy C, Grignon DJ, Sarkar FH, Sakr WA, Littrup P, Forman J. Expression of bcl-2, p53, and p21 in benign and malignant prostatic tissue before and after radiation therapy. Mod Pathol 1998; 11: 892-899.
  60. Marreiros A, Dudgeon K, Dao V, Grimm MO, Czolij R, Crossley M, Jackson P. KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells. Oncogene 2005; 24(4): 637-649. Go to original source... Go to PubMed...
  61. Cordon-Cardo C. Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol 1995; 147: 545-560.
  62. Macri E, Loda M. Role of p27 in prostate carcinogenesis. Cancer Metastasis Rev 1998; 17: 337-344. Go to original source... Go to PubMed...
  63. Fernandez PL, Arce Y, Farre X, Martinez A, Nadal A, Rey MJ, Peiro N, Campo E, Cardesa A. Expression of p27/ Kipl is down-regulated in human prostate carcinoma progression. J Pathol 1999; 187: 563-566. Go to original source... Go to PubMed...
  64. Cheville JC, Lloyd RV, Sebo TJ, Cheng L, Erickson L, Bostwick DG, Lohse CM, Wollan P. Expression of p27kipl in prostatic adenocarcinoma. Mod Pathol 1998; 11: 324-328.
  65. Tsihlias J, Kapusta LR, DeBoer G, Morava-Protzner I, Zbieranowski I, Bhattacharya N, Catzavelos GC, Klotz LH, Slingerland JM. Loss of cyclin-dependent kinase inhibitor p27Kipl is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res 1998; 58: 542-548.
  66. Vis AN, van Rhijn BW, Noordzij MA, Schroder FH, van der Kwast TH. Value of tissue markers p27(kipl), MIB-1,and CD44s for the preoperative prediction of tumour features in screen detected prostate cancer. J Pathol 2002; 197: 148-154. Go to original source... Go to PubMed...
  67. Freedland SJ, deGregorio F, Sacoolidge JC, Elshimali I, Csathy GS, Dorey F, Reiter RE, Aronson WJ. Preoperative p27 status is an independent predictor of prostate specific antigen failure following radical prostatectomy. J Urol 2003; 169: 1325-1330. Go to original source... Go to PubMed...
  68. Koivisto PA, Rantala I. Amplification of the androgen receptor gene is associated with P53 mutation in hormone-refractory recurrent prostate cancer. J Pathol 1999; 187: 237-241. Go to original source... Go to PubMed...
  69. Revelos K, Petraki C, Gregorakis A, Scorilas A, Papanastasiou P, Tenta R, Koutsilieris M. P27(kipl) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer. In Vivo 2005; 19: 911-920.
  70. Rubio J, Ramos D, Lopez-Guerrero JÁ, Iborra I, Collado A, Solsona E, Almenar S,Llombart-Bosch A. Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/ Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens. Eur Urol 2005; 48: 745-751. Go to original source... Go to PubMed...
  71. Borre M, Bentzen SM, Nerstrom B, Overgaard J. Tumor cell proliferation and survival in patients with prostate cancer followed expectantly. J Urol 1998; 159: 1609-1614. Go to original source... Go to PubMed...
  72. Carrol PR, Waldman FM, Rosenau W et al. Cell proliferation in prostatic adenocarcinoma: In vitro measurement by 5- bromodeoxyuridine incorporation and proliferating cell nuclear antigen expression. J Urol 1993; 149: 403-407. Go to original source... Go to PubMed...
  73. Xiang G, Porter AT, Gringon DJ. Diagnostic and prognostic Markers for Human Prostate Cancer. The Prostate 1997; 31: 264-281. Go to original source... Go to PubMed...
  74. Mori R,Wang Q, Quek ML, Tarabolous C, Cheung E,Ye W, Groshen S, Hawes D, Togo S, Shimada H, Danenberg KD, Danenberg PV, Pinski JK. Prognostic value of the androgen receptor and its coactivators in patients with prostate cancer. Anticancer Res 2008; 28(1B): 425-330.
  75. Augustin H,Hammerer PG,Graefen M,Palisaar J,Daghofer F,Huland H, Erbersdobler A. Characterisation of bio-molecular profiles in primary high-grade prostate cancer treated by radical prostatectomy. J Cancer Res Clin Oncol 2003; 129: 662-668. Go to original source... Go to PubMed...
  76. Cheng L, Nagabhushan M, Pretlow TP, Amini SB, Pretlow TG. Expression of E-cadherin in primary and metastatic prostate cancer. Am J Pathol 1996; 148: 1375-1380.
  77. Patriarca C, Petrella D, Campo B, Colombo P, Giunta P, Parente M, Zucchini N, Mazzucchelli R, Montironi R. Elevated E-cadherin and alpha/beta-catenin expression after androgen deprivation therapy in prostate adenocarcinoma. Pathol Res Pract 2003; 199: 659-665. Go to original source... Go to PubMed...
  78. Aaltomaa S, Lipponen P, Ala-Opas M, Eskelinen M, Kosma VM. Alpha-catenin expression has prognostic value in local and locally advanced prostate cancer. Br J Cancer 1999; 80: 477-482. Go to original source... Go to PubMed...
  79. Bostwick DG, Qian J, Pacelli A, Zincke H, Blute M, Bergstralh EJ, Slezak JM, Cheng L. Neuroendocrine expression in node positive prostate cancer: correlation with systemic progression and patient survival. J Urol 2002; 168: 1204-1211. Go to original source... Go to PubMed...
  80. Theodorescu D, Broder SR, Boyd JC, Mills SE, Frierson HF Jr. Cathepsin D and chromogranin A as predictors of long-term disease specific survival after radical prostatectomy for localized carcinoma of the prostate. Cancer 1997; 80: 2109-2119. Go to original source... Go to PubMed...
  81. Cindolo L, Cantile M, Vacherot F, Terry S, de la Taille A. Neuroendocrine differentiation in prostate cancer: from lab to bedside. Urol Int. 2007; 79(4): 287-296. Go to original source... Go to PubMed...
  82. Mack B, Gires O. CD44s and CD44v6 expression in head and neck epithelia. PLoS ONE 2008; 3(10): e3360 [Epub 2008 Oct 9]. Go to original source... Go to PubMed...
  83. Bussemakers MJ, van Bockhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA. DD3: a new prostate-specific gene,highly overexpressed in prostate cancer. Cancer Res 1999; 59(23): 5975-5979.
  84. De Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 2002; 62(9): 2696-2698.
  85. Meng FJ, Shan A, Jin L, Young CY. The expression of a variant prostate-specific antigen in human prostate. Cancer Epidemic Biomarkers Prev 2002; 11(3): 305-309.
  86. Moul JW. Angiogenesis, p53, bcl-2 and Ki-67 in the progression of prostate cancer after radical prostatectomy. Eur Urol 1999; 35(5-6): 399-407. Go to original source... Go to PubMed...

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