Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues

Prostate Cancer and Prostatic Diseases volume 6, pages 223–227 (2003)Cite this article

Abstract

Human kallikreins 6, 10 and 13 (hK6, hK10 and hK13) are expressed by many normal, mainly glandular tissues, including prostatic epithelium. Some kallikreins may function as tumor suppressors or are downregulated during cancer progression. The aim of this study was to evaluate the immunoexpression of these kallikreins in benign and malignant prostatic tissues and correlate their expression with prostate cancer (PC) prognosis. Included in the study were 25 cases of nonmalignant prostate and 179 cases of PC. Among them, 122 PC cases were immunostained for hK6, 94 for hK10 and 113 for hK13, respectively. The follow-up period for a subset of 68 patients who had undergone radical prostatectomy (RP) was 1–58 months (mean=13.4±1.7 and median=8.0 months). A cutoff value of 0.2 μg/l of serum PSA was established as a biochemical recurrence threshold. Follow-up information was available for 26/55 RP cases stained for hK6, 14/32 cases stained for hK10 and 25/59 cases stained for hK13. Gleason score (GS) 7 carcinomas were stratified as 7a and 7b, according to the primary grade. PC with GS 2–7a were histologically categorized as low malignant (LM) and PC with GS 7b–10 as high malignant (HM). The immunohistochemical method of streptavidin–biotin–peroxidase using monoclonal and polyclonal antibodies was performed. In the benign prostate and in prostatic intraepithelial neoplasia, a cytoplasmic immunostaining of varying intensity was evident. In PC, the immunoexpression of all kallikreins was decreased: 102/122 cases (84%) were positive for hK6, 73/94 (78%) for hK10 and 97/113 (86%) for hK13, respectively. A statistically significant difference in expression was found, in comparison to nonmalignant prostates (P=0.029, 0.009 and 0.045, respectively). Also, a positive correlation was observed between the immunoexpression of these three kallikreins. Concerning the histological grade, HM-PC expressed all three kallikreins with a slightly higher percentage than LM-PC: 79 vs 88% for hK6, 76 vs 79% for hK10 and 76 vs 92% for hK13. These differences were statistically significant only in the case of hK13 (P=0.024). Serum PSA did not correlate with kallikrein immunoexpression in PC. Furthermore, there was no significant correlation between kallikrein expression and pathological stage or recurrence, in the cases of RP. All three kallikreins are expressed in the nonmalignant and malignant prostate, with cancer tissues demonstrating slightly lower expression. Expression levels did not correlate with aggressiveness and they do not seem to have value for prostate cancer prognosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Diamandis EP et al. The human kallikrein gene family: implications in carcinogenesis. Trends Endocrinol Metab 2000; 11: 54–60.

    Article  CAS  PubMed  Google Scholar 

  2. Yousef GM, Diamandis EP . The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001; 22: 184–204.

    CAS  PubMed  Google Scholar 

  3. Petraki C et al. The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression in human tissues, as assessed by immunohistochemistry. J Histochem Cytochem 2001; 49: 1431–1442.

    Article  CAS  PubMed  Google Scholar 

  4. Petraki C et al. Human kallikrein 10 expression in normal tissues by immunohistochemistry. J Histochem Cytochem 2002; 50: 1247–1261.

    Article  CAS  PubMed  Google Scholar 

  5. Petraki CD, Karavana VN, Diamandis EP . Human kallikrein 13 expression in normal tissues: an immunohistochemical study. J Histochem Cytochem 2003; 51: 493–501.

    Article  CAS  PubMed  Google Scholar 

  6. Gleason DF . Histologic grading of prostatic carcinoma. In: Bostwick, DG (ed). Pathology of the Prostate. Churchill Livingstone, New York, Edinburgh, London, Melbourne, 1990, pp 83–93.

    Google Scholar 

  7. Diamandis EP et al. Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications. Clin Biochem 2000; 33: 369–375.

    Article  CAS  PubMed  Google Scholar 

  8. Luo LY et al. Immunofluorometric assay of human kallikrein 10 and its identification in biological fluids and tissues. Clin Chem 2001; 47: 237–246.

    CAS  PubMed  Google Scholar 

  9. Kapadia C et al. Human kallikrein 13: production and purification of recombinant protein, monoclonal and polyclonal antibodies, and development of a sensitive and specific immunofluorometric assay. Clin Chem 2003; 49: 77–86.

    Article  CAS  PubMed  Google Scholar 

  10. Oesterling JE . Prostate-specific antigen. The best prostatic tumor marker. Urol Clin N Am 1997; 24: 247–458.

    Article  Google Scholar 

  11. Rittenhouse HG et al. Human kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci 1998; 35: 275–368.

    Article  CAS  PubMed  Google Scholar 

  12. Becker C et al. The role of molecular forms of prostate-specific antigen (PSA or hK3) and of human glandular kallikrein 2 (hK2) in the diagnosis and monitoring of prostate cancer and in extra-prostatic disease. Crit Rev Clin Lab Sci 2001; 38: 357–399.

    Article  CAS  PubMed  Google Scholar 

  13. Stephan C et al. Prostate-specific antigen, its molecular forms, and other kallikrein markers for detection of prostate cancer. Urology 2002; 59: 2–8.

    Article  PubMed  Google Scholar 

  14. Recker F et al. Human glandular kallikrein as a tool to improve discrimination of poorly differentiated and non-organ-confined prostate cancer compared with prostate-specific antigen. Urology 2000; 55: 481–485.

    Article  CAS  PubMed  Google Scholar 

  15. Nam RK et al. Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen. J Clin Oncol 2000; 18: 1036–1042.

    Article  CAS  PubMed  Google Scholar 

  16. Obiezu CV et al. Detection of human kallikrein 4 in healthy and cancerous prostatic tissues by immunofluorometry and immunohistochemistry. Clin Chem 2002; 48: 1232–1240.

    CAS  PubMed  Google Scholar 

  17. Yousef GM et al. Molecular cloning of the human kallikrein 15 gene (KLK15): upregulation in prostate cancer. J Biol Chem 2001; 276: 53–61.

    Article  CAS  PubMed  Google Scholar 

  18. Diamandis EP et al. Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma. Cancer Res 2002; 62: 295–300.

    CAS  PubMed  Google Scholar 

  19. Darson MF et al. Human glandular kallikrein 2 (hK2) expression in prostate intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. Urology 1997; 49: 857–862.

    Article  CAS  PubMed  Google Scholar 

  20. Darson MF et al. Human glandular kallikrein 2 expression in prostate adenocarcinoma and lymph node metastases. Urology 1999; 53: 939–944.

    Article  CAS  PubMed  Google Scholar 

  21. Maglara A et al. Decreased concentration of prostate-specific antigen and human glandular kallikrein 2 in malignant versus nonmalignant prostatic tissue. Urology 2000; 56: 527–532.

    Article  Google Scholar 

  22. Pretlow TG et al. Tissue concentrations of prostate-specific antigen in prostatic carcinoma and benign prostatic hyperplasia. Int J Cancer 1991; 49: 645–649.

    Article  CAS  PubMed  Google Scholar 

  23. Diamandis EP et al. Human kallikrein 6 (zyme/protease M/neurosin): a new serum biomarker of ovarian carcinoma. Clin Biochem 2000; 33: 579–583.

    Article  CAS  PubMed  Google Scholar 

  24. Luo L-Y et al. Human kallikrein 10: a novel tumor marker for ovarian carcinoma? Clin Chim Acta 2001; 306: 111–118.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants to EP Diamandis from the National Cancer Institute of Canada, the National Institutes of Health, USA and by a University-Industry grant from the Natural Sciences and Engineering Research Council of Canada and ONCOTherapeutics Inc.

Author information

Authors and Affiliations

  1. Departments of Pathology and Urology, Evangelismos Hospital, Athens, Greece

    C D Petraki, A K Gregorakis, P A Papanastasiou & V N Karavana

  2. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, M5G 1X5, Ontario, Canada

    L-Y Luo & E P Diamandis

  3. Department of Laboratory Medicine and Pathobiology, University of Toronto, M5G 1L5, Ontario, Canada

    L-Y Luo & E P Diamandis

Authors
  1. C D Petraki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A K Gregorakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P A Papanastasiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V N Karavana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L-Y Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E P Diamandis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E P Diamandis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petraki, C., Gregorakis, A., Papanastasiou, P. et al. Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues. Prostate Cancer Prostatic Dis 6, 223–227 (2003). https://doi.org/10.1038/sj.pcan.4500674

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4500674

Keywords

This article is cited by

Search

Advanced search

Quick links