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Prostatic fluid electrolyte composition for the screening of prostate cancer: a potential solution to a major problem

Abstract

Early detection is the key to effective treatment of prostate cancer, and to the prevention of deaths due to progression to untreatable advanced stage cancer. Because of mitigating factors, especially benign prostatic hyperplasia (BPH), that result in a low accuracy (about 60%) of prostate-specific antigen (PSA) testing, there is an urgent need for a more reliable biomarker for the identification of early stage through advanced stage prostate cancer and ‘at-risk’ individuals. To address this issue we propose that changes in prostatic fluid composition could provide accurate and reliable biomarkers for the screening of prostate cancer. Most notable is the consistent and significant decrease in citrate and zinc that is associated with the development and progression of prostate cancer. In this review we provide the clinical and physiological basis and the evidence in support of the utility of prostatic fluid analysis as an effective approach for screening/detection of prostate cancer, especially early stage and ‘at-risk’ subjects. The problem of BPH interference that plagues PSA testing is eliminated in the potential prostatic fluid biomarkers. The potential development of rapid, simple, direct, accurate clinical tests provides additional advantageous conditions. Further exploration and development of citrate, zinc and other electrolytes as prostatic fluid biomarkers are urgently needed to address this critical prostate cancer issue.

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References

  1. Carter H, DeMarzo A, Lilja H . Detection, Diagnosis, and Prognosis of Prostate Cancer. Prostate Cancer Foundation Report to the Nation on Prostate Cancer 2004, 9–26.

  2. Stamey TA, Caldwell M, McNeal JE, Nolley R, Hemenez M, Downs J . The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004; 172: 1297–1301.

    Article  PubMed  Google Scholar 

  3. Costello LC, Franklin RB . Citrate metabolism in prostate and other cancers. In: Singh K, Costello LC (eds). Mitochondria and Cancer. Springer: New York, (in press).

  4. Costello LC, Franklin RB . The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots. Mol Cancer 2006; 5: 17.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Costello LC, Franklin RB . The metabolism of prostate malignancy: insights into the pathogenesis of prostate cancer and new approaches for its diagnosis and treatment. Oncol Spectr 2001; 2: 452–457.

    Google Scholar 

  6. Franklin RF, Costello LC . Zinc as an anti-tumor agent in prostate cancer and in other cancers. Arch Biochem Biophys 2007; 463: 211–217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Franklin RB, Milon B, Feng P, Costello LC . Zinc and zinc transporter in normal prostate function and the pathogenesis of prostate cancer. Front Biosci 2005; 10: 2230–2239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scherstén B . Uber das vorkommen der zitronensäure in geschlechtsdrusensekreton. Skand Arch Physiol 1929; 58: 90.

    Article  Google Scholar 

  9. Huggins C . The prostatic secretions. Harvey Lect 1946; 42: 148–193.

    Google Scholar 

  10. Kavanagh JP . Sodium, potassium, calcium, magnesium, zinc, citrate and chloride content of human prostatic and seminal fluid. J Reprod Fertil 1985; 75: 35–41.

    Article  CAS  PubMed  Google Scholar 

  11. Averna TA, Kline EE, Smith AY, Sillerud LO . A decrease in 1H nuclear magnetic resonance spectroscopically determined citrate in human seminal fluid accompanies the development of prostate adenocarcinoma. J Urol 2005; 173: 433–438.

    Article  PubMed  Google Scholar 

  12. Kline EE, Treat EG, Averna TA, Davis MS, Smith AY, Sillerud LO . Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection. J Urol 2006; 176: 2274–2279.

    Article  CAS  PubMed  Google Scholar 

  13. Serkova NJ, Gamito EJ, Jones RH, O'Donnell C, Brown JL, Green S et al. The metabolites citrate, myo-inositol, and spermine are potential age-independent markers of prostate cancer in human expressed prostatic secretions. Prostate 2008; 68: 620–628.

    Article  CAS  PubMed  Google Scholar 

  14. Zaichick VY, Sviridova TV, Zaichick SV . Zinc concentration in human prostatic fluid: normal, chronic prostatitis, adenoma and cancer. Int Urol Nephrol 1996; 28: 687–694.

    Article  CAS  PubMed  Google Scholar 

  15. Mawson CA, Fischer MI . The occurrence of zinc in the human prostate gland. Can J Med Sci 1952; 30: 336–339.

    CAS  PubMed  Google Scholar 

  16. Costello LC, Franklin RB, Narayan P . Citrate in the diagnosis of prostate cancer. Prostate 1999; 38: 237–245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Costello L, Franklin RB, Kurhanewicz J . The metabolic characterization of prostate malignancy by magnetic resonance spectroscopy. In: Pertino J (ed) Encyclopedia of Cancer, 2nd edn., vol 3, Elsevier Science: USA, 2002, pp 167–177.

    Chapter  Google Scholar 

  18. Kurhanewicz J, Swanson MG, Nelson SJ, Vigneron DB . Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer. J Magn Reson Imaging 2002; 16: 451–463.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Cooper JE, Farid I . 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 1964; 92: 533–536.

    Article  CAS  PubMed  Google Scholar 

  20. Habib FK, Mason MK, Smith PH, Stitch SR . Cancer of the prostate: early diagnosis by zinc and hormone analysis. Br J Cancer 1979; 39: 700–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen J, Xu Z, Zhao H, Jiang X . Citrate in expressed prostatic secretions has the feasibility to be used as a useful indicator for the diagnosis of category IIIB prostatitis. Urol Int 2007; 78: 230–234.

    Article  CAS  PubMed  Google Scholar 

  22. Kavanagh JP, Darby C, Costello CB . The response of seven prostatic fluid components to prostatic disease. Int J Androl 1982; 5: 487–496.

    Article  CAS  PubMed  Google Scholar 

  23. Zakian KL, Eberhardt S, Hricak H, Shukla-Dave A, Kleinman S, Muruganandham M et al. Transition zone prostate cancer: metabolic characteristics at 1H MR spectroscopic imaging--initial results. Radiology 2003; 229: 241–247.

    Article  PubMed  Google Scholar 

  24. Kurhanewicz J, Vigneron DB, Hricak H, Narayan P, Carroll P, Nelson SJ . Three dimensional hydrogen-1 MR spectroscopic imaging of the in situ human prostate with (0.24–0.7-cm3) high spatial resolution. Radiology 1996; 198: 795–805.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Data were obtained from studies supported by NIH grants CA79903, CA093443, CA71207.

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Correspondence to L C Costello.

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Costello, L., Franklin, R. Prostatic fluid electrolyte composition for the screening of prostate cancer: a potential solution to a major problem. Prostate Cancer Prostatic Dis 12, 17–24 (2009). https://doi.org/10.1038/pcan.2008.19

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