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Realizing the Potential of Ejaculate/Seminal Fluid in Detecting and Predicting Natural History

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Prostate Cancer Methods and Protocols

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 81))

Abstract

The widespread acceptance of prostate-specific antigen (PSA) testing by clinicians as evidence of prostatic pathology and recognition that elevated levels in serum often precede overt disease has permitted a much earlier identification of patients with prostatic epithelial changes, particularly cancer. Prostate cancer patients thus identified are very often asymptomatic with clinically benign prostates on digital rectal examination.

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References

  1. Presti, J. C. Jr, Chang, J. J., Bhargava, V., and Shinohara, K. (2000) The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: Results of a prospective clinical trial. J. Urol. 163, 163ā€“166.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  2. Brossner, C., Bayer, G., Madersbacher, S., Kuber, W., Klingler, C., and Pycha, A. (2000) Twelve prostate biopsies detect significant cancer volumes (>0.5 mL). BJU Int. 85, 705ā€“707.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  3. Naughton, C. K., Miller, D. C., Mager, D. E., Ornstein, D. K., and Catalona, W. J. (2000) A prospective randomized trial of 6 versus 12 prostate biopsy cores: Impact on cancer detection. J. Urol. 164, 388ā€“392.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  4. Partin, A. W., Kattan, M. W., Subong, E. N., Walsh, P. C., Wojno, K. J., Oesterling, J. E., Scardino, P. T. and Pearson, J. D. (1997) Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA 277, 1445ā€“1451.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  5. Catalona, W. J., Partin, A. W., Slawin, K. M., Brawer, M. K., Flanigan, R. C., Patel, A., et al. (1998) Percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: A prospective multicenter clinical trial. JAMA 279, 1542ā€“1547.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  6. Djavan, B., Zlotta, A. R., Byttebier, G., Shariat, S., Omar, M., Schulman, C. C., and Marberger, M. (1998) Prostate specific antigen density of the transition zone for early detection of prostate cancer. J. Urol. 160, 411ā€“419.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  7. Djavan, B., Zlotta, A., Kratzik, C., Remzi, M., Seitz, C., Schulman, C. C., and Marberger, M. (1999) PSA, PSA density, density of transition zone, free/total PSA ratio & PSA velocity for early detection of prostate cancer in men with serum PSA 2.5 to 4.0 ng/ml. Urology 54, 517ā€“522.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  8. Djavan, B., Zlotta, A. R., Remzi, M., Ghawidel, K., Bursa, B., Hruby, S., et al. (1999) Total & transition zone prostate volume and age: how do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection? Urology 54, 846ā€“852.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  9. Gardiner, R. A., Samaratunga, M. L. T. H., Gwynne, R. A., Clague, A., Seymour, G. J. S., and Lavin, M. F. (1996) Abnormal prostatic cells in ejaculates from men with prostatic cancerā€”a preliminary report. Br. J. Urol. 78, 414ā€“418.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  10. Gardiner, R. A., Samaratunga, M. L. T. H., Rohde, P., Clements, J. A., Hyland, V., and Lavin, M. F. (1997) Re: malignant cytological washings from radical prostatectomy specimens: A possible mechanism for local recurrence of prostate cancer following surgical treatment of organ confined disease (letter). J. Urol. 158, 889.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  11. Barren, R. J. III, Holmes, E. H., Boynton, A. L., Gregorakis, A., Abdel-Aziz, A., Cobb, O. E., et al. (1998) Method for identifying prostate cells in semen using flow cytometry. Prostate 36, 181ā€“188.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  12. Clements, J. A., Rohde, P., Allen, V., Hyland, V. J., Samaratunga, M. L. T. H., Tilley, W. D., et al. (1999) Molecular detection of prostate cells in ejaculate and urethral washings in men with suspected prostate cancer. J. Urol. 61, 1337ā€“1343.

    Google ScholarĀ 

  13. Shen, R., Su, Z. Z., Olsson, C. A., and Fisher, P. B. (1995) Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display. Proc. Natl. Acad. Sci. USA 92, 6778ā€“6782.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  14. Li, S. L., Goko, H., Xu, Z. D., Kimura, G., Sun, Y., Kawachi, M. H., et al. (1998) Insulin like growth factor 1 in human prostate, breast, bladder & paraganglioma tumors. Cell Tissue Res. 291, 469ā€“479.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  15. Mantzoros, C. S., Tzonou, A., Signorello, L. B., Stampfer, M., Trichopoulos, D., and Adami, H. O. (1997) Insulin like growth factor 1 in relation to CaP and BPH. Br. J. Cancer 76, 1115ā€“1118.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  16. Bentley, H., Hambdy, F. C., Hart, K. A., Seid, J. M., Williams, J. L., Johnstone, D., and Russell, R. G. (1992) Expression of bone morphognenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. Br. J. Cancer 66, 1159ā€“1163.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  17. Harris, S. E., Harris, M. A, Mahy, P., Wozney, J., Feng, J. Q., and Mundy, G. R. (1994) Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells. Prostate 24, 204ā€“211.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  18. Hambdy, F. C., Autzen, P., Robinson, M. C., Home, C. H., Neal, D. E., and Robson, C. N. (1997) Immunolocalization and messenger RNA expression of bone morpho-genetic protein-6 in human benign and malignant prostatic tissue. Cancer Res. 57, 4427ā€“4431.

    Google ScholarĀ 

  19. Barnes, J., Anthony, C. T., Wall, N., and Steiner, M. S. (1995) Bone morpho-genetic protein-6 expression in normal and malignant prostate. World J. Urol. 13, 337ā€“343.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  20. Sinisi, A. A., Bellastella, A., Prezioso, D., Nicchio, M. R., Lotti, T., Salvatore, M., et al. (1997) Different expression patterns of somatostatin receptor subtypes in cultured epithelial cells from human normal prostate and prostate cancer. J. Clin. Endocrinol. Metab. 82, 2566ā€“2569.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  21. Burger, M..J., Mould, M., Samaratunga, H.M., Clements, J., Lavin, M.F., and Gardiner, R.A. (2002) Expression analysis of Ī“-catenin and prostate specific membrane antigen; their potential as diagnostic markers for Prostate Cancer. Int. J. Cancer 100, 228ā€“237.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  22. Rittenhouse, H. G., Finlay, J. A., Mikolajczyk, S. D., and Partin A. W. (1998) Human kallikrein 2 (hK2) and prostate-specific antigen (PSA): Two closely related, but distinct, kallikreins in the prostate. Crit. Rev. Clin. Lab. Sci. 35, 275ā€“368.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  23. Lilja, H., Oldbring, J., Rannevik, G., and Laurell, C.-B. (1987) Seminal vesicle-secreted proteins anda their reactions during gelation and liquefaction of human semen. J. Clin. Invest. 80, 281ā€“285.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  24. Christensson, A. and Lilja, H. (1994) Complex formation between protein C inhibitor and prostate specific antigen in vitro and in human semen. Eur. J. Biochem. 220, 45ā€“53.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  25. Otto, A., Bar, J., and Birkenmeier, G. (1998) Prostate-specific antigen forms complexes with human-Ī±2-macroglobulin and binds to the-Ī±2-macroglobulin receptor-related protein. J. Urol. 159, 297ā€“303.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  26. Permanetter, W. and Meister, P. (1984) Distribution of lysozyme (muraminidase) and (1-antichymotrypsin in normal and neoplastic epithelial tissues: a survey. Acta Histochem. 74, 173ā€“179.

    PubMedĀ  CASĀ  Google ScholarĀ 

  27. Bjork, T., Hulkko, S., Bjartell, A., di Santā€™gnese, A., Abrahamsson, P.-A., and Lilja H. (1994) Ī±1-antichymotrypsin production in PSA-producing cells is common in prostate cancer but rare in benign prostatic hyperplasia. Urology 43, 427ā€“433.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  28. Qian, Y., Sensibar, J. A., Zelner, D. J., Schaeffer, A. J., Finlay, J. A., Rittenhouse, H. G., and Lee, C. (1997) Two-dimensional gel electrophoresis detects prostate-specific antigen-Ī±1-antichymotrypsin complex in serum but not prostatic fluid. Clin. Chem. 43, 352ā€“359.

    PubMedĀ  CASĀ  Google ScholarĀ 

  29. Clements, J. A., Merritt, T., Devoss, K., Swanson, C., Hamlyn, L., Scells, B., et al. (2000) Inactive free:total prostate specific antigen ratios in ejaculate from men with suspected and known prostate cancer, compared with young control men. BJU Int. 86, 453ā€“458.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  30. Wang, Z., Ramin, S. A., Tsai, C., Lui, P., Herbert, P. J., Kyeyune-Nyombi, E., et al. (2001) Detection of telomerase activity in prostatic fluid specimens. Urol. Oncol. 6, 4ā€“9.

    ArticleĀ  CASĀ  Google ScholarĀ 

  31. Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., et al. (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011ā€“2015.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  32. Suh, C. I., Shanafelt, T., May, D. J., Shroyer, K. R., Bobak, J. B., Crawford, E. D., et al. (2000) Comparison of telomerase and GSTP1 promoter methylation in ejaculate, potential screening for prostate cancer. Mol. Cell Probes 14, 211ā€“217.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  33. Lynch, M. J. and Nicholson, J. K. (1997) Proton MRS of human prostatic fluid: Correlations between citrate, spermine and myo-inositol levels and change with disease. Prostate 3, 248ā€“255.

    ArticleĀ  Google ScholarĀ 

  34. Liu, H., Moy, P., Kim, S., Xia, Y., Rajasekaran, A., Navarro, V., et al. (1997) Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res. 57, 3629ā€“3634.

    PubMedĀ  CASĀ  Google ScholarĀ 

  35. Chang, S. S., Reuter, V. E., Heston, W. D., Bander, N. H., Grauer, L. S., and Gaudin, P. B. (1999) Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res. 59, 3192ā€“3198.

    PubMedĀ  CASĀ  Google ScholarĀ 

  36. Silver, D. A., Pellicer, I., Fair, W. R., Heston, W. D., and Cordon-Cardo, C. (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin. Cancer Res. 3, 81ā€“85.

    PubMedĀ  CASĀ  Google ScholarĀ 

  37. Jassim, A. and Festenstein, H. (1987) Immunological and morphological characterisation of nucleated cells other than sperm in semen of oligospermic donors. J. Reprod. Immunol. 11, 77ā€“89.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  38. Sharifi, R., Rhee, H., Shaw, M., Nagubadi, S., Ray, V., and Guinan, P. (1983) Evaluation of cytologic techniques for diagnosis of prostatic cancer. Urology 21, 417ā€“420.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  39. Berry, S. J., Coffey, D. S., Walsh, P. C., and Ewing, L. L. The development of human benign prostatic hyperplasia with age. J. Urol. 132, 474ā€“479.

    Google ScholarĀ 

  40. Israeli, R. S., Powell, C. T., Fair, W. R., and Heston, W. D. (1993) Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 227, 227ā€“230.

    Google ScholarĀ 

  41. Wright, G. L. Jr, Beckett, M. L., Lipford, G. B., Haley, C. L., and Schellhammer, P. F. (1991) A novel prostate carcinoma-associated glycoprotein complex (PAC) recognized by monoclonal antibody TURP-27. Int. J. Cancer 47, 717ā€“725.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  42. Kim, Y. D., Robinson, D. Y., and Tomita, J. T. (1888) Monoclonal antibody PR92 with restricted specificity for tumor-associated antigen of prostate and breast carcinoma. Cancer Res. 48, 4543ā€“4548.

    Google ScholarĀ 

  43. Emmert-Buck, M. R., Strausberg, R. L., Krizman, D. B., Bonaldo, M. F., Bonner, R. F., Bostwick, D. G., et al. (2000) Molecular profiling of clinical tissue specimens: feasibility and applications. Am. J. Pathol. 156, 1109ā€“1115.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  44. Foster, C. S., Bostwick, D. G., Bonkoff, H., Damber, J.-E., van der Kwast, T., Montironi, R., and Sakr, W. A. (2000) Cellular and molecular pathology of prostate cancer precursors: WHO Consensus Conference June 8ā€“9 2000. Scand. J. Urol. Nephrol. 34, 18ā€“43.

    ArticleĀ  Google ScholarĀ 

  45. Liu, X. H., Kirschenbaum, A., Yao, S., Stearns, M. E., Holland, J. F., Claffey, K., and Levine, A. C. (1999) Upregulation of vascular endothelial growth factor by cobalt chloride-simulated hypoxia is mediated by persistent induction of cyclooxy-genase-2 in a metastatic human prostate cancer cell line. Clin. Exp. Metastasis 17, 687ā€“694.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  46. Chen, H. J., Treweeke, A. T., Ke, Y. Q., West, D. C., and Toh, C. H. (2000) Angio-genically active vascular endothelial growth factor is over-expressed in malignant human and rat prostate carcinoma cells. Br. J. Cancer 82, 1694ā€“1701.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  47. Collett, G. P., Betts, A. M., Johnson, M. I., Pulimood, A. B., Cook, S., Neal, D. E., et al. (2000) Peroxisome proliferator-activated receptor alpha is an androgen-responsive gene and is highly expressed in prostatic adenocarcinoma. Clin. Cancer Res. 6, 3241ā€“3248.

    PubMedĀ  CASĀ  Google ScholarĀ 

  48. Tavtigian, S. V., Simard, J., Teng, D. H., Abtin, V., Baumgard, M., Beck, A., et al. (2001) A candidate prostate cancer susceptibility gene at chromosome 17p. Nat. Genet. 27, 172ā€“180.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  49. de Kok, J.B., Verhaegh, G.W., Roelofs, R.W., Hessels, D., Kiemeney, B.A., Aalders, T.W., et al. (2002) DD3 (PCA3), a very sensitive and specific marker to detect prostate cancer. Cancer Res 62, 2695ā€“2698.

    PubMedĀ  Google ScholarĀ 

  50. Nelson, J.B., Chan-Tack, K., Hedican, S.P., Magnuson, S.R., Opgenorth, T.J., Bova, G.S., Simons, J. W. (1996) Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. Cancer Res 56, 663ā€“668.

    PubMedĀ  CASĀ  Google ScholarĀ 

  51. Gohji, K., Kitazawa, S., Tamada, H., Katsuoka, Y., and Nakajima, M. (2001) Expression of endothelin receptor A associated with prostate cancer progression. J. Urol. 165, 1033ā€“1036.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  52. Holgersson, J., Pimlott, W., Samuelsson, B. E., and Breimer, M. E. (1989) Electron ionization mass spectrometry for sequence analysis of glycosphingolipid mixtures by fractional evaporation in the ion source. Mass spectrometric evidence for an eleven-sugar glycolipid. Rapid Commun. Mass Spectrom. 3, 400ā€“404.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  53. Costello, C. E. and Vath, J. E. (1990) Tandem mass spectrometry of glycolipids. Meth. Enzymol. 193, 738ā€“768.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  54. Dell, A. (1990) Preparation and desorption mass spectometry of permethyl and peracetyl derivatives of oligosaccharides. Meth. Enzymol. 193, 647ā€“660.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  55. Favretto, D., Seraglia, R., Traldi, P., Curcuruto, O., and Hamdan, M. (1994) Electrospray vs. matrix-assisted laser desorption/ionization I. Some examples in the protein field. Organic Mass Spectrom. 29, 526ā€“532.

    ArticleĀ  CASĀ  Google ScholarĀ 

  56. Perreult, H. and Costello, C. E. (1994) Liquid secondary ionization, tandem and matrix-assisted laser desorption/ionization time-of-flight mass spectrometric characterization of glycosphingolipid derivatives. Organic Mass Spectrom. 29, 720ā€“735.

    ArticleĀ  Google ScholarĀ 

  57. Costello, L. C. and Franklin, L. B. (1991) Concepts of citrate production secretion by the prostate. 1. Metabolic relationships. Prostate 18, 25ā€“46.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  58. Costello, L. C., Franklin, R. B., and Narayan, P. (1999) Review article: citrate in the diagnosis of prostate cancer. Prostate 38, 237ā€“245.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  59. Cooper, J. F. and Imheld, H. (1959) The role of citric acid in the physiology of the prostate; a preliminary report. J. Urol. 81, 157ā€“163.

    PubMedĀ  CASĀ  Google ScholarĀ 

  60. Marberger, H., Marberger, E., Mann, T., and Lutwak-Mann, C. (1962) Citric acid in human prostatic secretion and metastasizing cancer of the prostate gland. Br. Med. J. 1, 835ā€“836.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  61. Cooper, J. E. and Farid, I. (1964) The role of citric acid in the physiology of the prostate. Lactic/citrate ratios in benign and malignant prostatic homogenates as an index of prostatic malignancy. J. Urol. 92, 533ā€“536.

    PubMedĀ  CASĀ  Google ScholarĀ 

  62. Scheibler, M. R., Miyamoto, K. K., White, M., Maygarden, S. J., and Mohler, J. L. (1993) In vivo high resolution 1H spectroscopy of the human prostate: Benign prostatic hyperplasia, normal peripheral zone and adenocarcinoma. Magn. Reson. Med. 29, 285ā€“291.

    ArticleĀ  Google ScholarĀ 

  63. Cornel, E. B., Smits, G. A. H. J., Oosterhof, G. O. N., Karthaus, H. F. M., Debruyne, F. M. J., Schalken, J. A., and Heerschap, A. (1993) Characterization of human prostate cancer, benign prostatic hyperplasia and normal prostate by in-vitro 1H and 3P magnetic resonance spectroscopy. J. Urol. 150, 2019ā€“2024.

    PubMedĀ  CASĀ  Google ScholarĀ 

  64. Kavanagh, J. P (1985) Sodium, potassium, calcium, magnesium, zinc, citrate and chloride content of human prostatic and seminal fluid. J. Reprod. Fertil. 75, 35ā€“41.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  65. Heerschap, A., Jager, G. J., van der Graaf, M., Barentz, J. O., De La Rosette, J. J., Oosterhof, G. O. N., et al. (1997) In vivo proton spectroscopy reveals altered metabolite content in malignant prostate tissue. Anticancer Res. 17, 1455ā€“1460.

    PubMedĀ  CASĀ  Google ScholarĀ 

  66. Anderson, R. U. and Fair, W. R. (1976) Physical and chemical determinations of prostatic secretion in benign hyperplasia, prostatitis and adenocarcinoma. Invest. Urol. 14, 133ā€“140.

    Google ScholarĀ 

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Gardiner, R.A., Burger, M., Clements, J.A., Lavin, M.F. (2003). Realizing the Potential of Ejaculate/Seminal Fluid in Detecting and Predicting Natural History. In: Russell, P.J., Jackson, P., Kingsley, E.A. (eds) Prostate Cancer Methods and Protocols. Methods in Molecular Medicineā„¢, vol 81. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-372-0:199

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  • DOI: https://doi.org/10.1385/1-59259-372-0:199

  • Publisher Name: Springer, Totowa, NJ

  • Print ISBN: 978-0-89603-978-0

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