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.

  • Original Article
  • Published:

Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression

Prostate Cancer and Prostatic Diseases volume 9, pages 279–283 (2006)Cite this article

Abstract

Objective: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed.

Patients and methods: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time.

Results: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=−0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=−0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022).

Conclusions: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.

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

Similar content being viewed by others

References

  1. Huggins C, Hodges C . Studies of prostatic cancer: I. Effect of castration, estrogen and androgen injections on serum phosphatase in metastatic carcinoma of the prostate. Cancer Res 1941; 1: 293–297.

    CAS  Google Scholar 

  2. Higano C, Shields A, Wood N, Brown J, Tangen C . Bone mineral density in patients with prostate cancer without bone metastases treated with intermittent androgen suppression. Urology 2004; 64: 1182–1186.

    Article  Google Scholar 

  3. Fossa SD, Woehre H, Kurth KH, Hetherington J, Bakke H, Rustad DA et al. Influence of urological morbidity on quality of life in patients with prostate cancer. Eur Urol 1997; 31 (Suppl 3): 3–8.

    Article  Google Scholar 

  4. Goldenberg SL, Bruchovsky N, Gleave ME, Sullivan LD, Akakura K . Intermittent androgen suppression in the treatment of prostate cancer: a preliminary report. Urology 1995; 45: 839–844.

    Article  CAS  Google Scholar 

  5. De La Taille A, Zerbib M, Conquy S, Amsellem-Ouazana D, Thiounn N, Flam TA et al. Intermittent androgen suppression in patients with prostate cancer. BJU Int 2003; 91: 18–22.

    Article  CAS  Google Scholar 

  6. Akakura K, Bruchovsky N, Goldenberg SL, Rennie PS, Buckley AR, Sullivan LD . Effects of intermittent androgen suppression on androgen-dependent tumours. Apoptosis and serum prostate-specific antigen. Cancer 1993; 71: 2782–2790.

    Article  CAS  Google Scholar 

  7. Sato N, Gleave ME, Bruchovsky N, Rennie PS, Goldenberg SL, Lange PH et al. Intermittent androgen suppression delays progression to androgen-independent regulation of prostate-specific antigen gene in the LNCaP prostate tumour model. J Steroid Biochem Mol Biol 1996; 58: 139–146.

    Article  CAS  Google Scholar 

  8. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649–655.

    Article  CAS  Google Scholar 

  9. Mostofi FK . Grading of prostatic carcinoma. Cancer Chemother Rep 1975; 59: 111–117.

    CAS  PubMed  Google Scholar 

  10. Sato N, Akakura K, Isaka S, Nakatsu H, Tanaka M, Ito H et al. Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study. Urology 2004; 64: 341–345.

    Article  Google Scholar 

  11. Sato N, Gleave ME, Bruchovsky N, Rennie PS, Beraldi E, Sullivan LD . A metastatic and androgen-sensitive human prostate cancer model using intraprostatic inoculation of LNCaP cells in SCID mice. Cancer Res 1997; 57: 1584–1589.

    CAS  PubMed  Google Scholar 

  12. Crook JM, Szumacher E, Malone S, Huan S, Segal R . Intermittent androgen suppression in the management of prostate cancer. Urology 1999; 53: 530–534.

    Article  CAS  Google Scholar 

  13. Grossfeld GD, Chaudhary UB, Reese DM, Carroll PR, Small EJ . Intermittent androgen deprivation: update of cycling characteristics in patients without clinically apparent metastatic prostate cancer. Urology 2001; 58: 240–245.

    Article  CAS  Google Scholar 

  14. Albrecht W, Collette L, Fava C, Kariakine OB, Whelan P, Studer UE et al. Intermittent maximal androgen blockade in patients with metastatic prostate cancer: an EORTC feasibility study. Eur Urol 2003; 44: 505–511.

    Article  CAS  Google Scholar 

  15. Prapotnich D, Fizazi K, Escudier B, Mombet A, Cathala N, Vallancien G . A 10-year clinical experience with intermittent hormonal therapy for prostate cancer. Eur Urol 2003; 43: 233–239.

    Article  Google Scholar 

  16. Koivisto P, Visakorpi T, Rantala I, Isola J . Increased cell proliferation activity and decreased cell death are associated with the emergence of hormone-refractory recurrent prostate cancer. J Pathol 1997; 183: 51–56.

    Article  CAS  Google Scholar 

  17. Paterson RF, Gleave ME, Jones EC, Zubovits JT, Goldenberg SL, Sullivan LD . Immunohistochemical analysis of radical prostatectomy specimens after 8 months of neoadjuvant hormonal therapy. Mol Urol 1999; 3: 277–286.

    CAS  PubMed  Google Scholar 

  18. Matsushima H, Goto T, Hosaka Y, Kitamura T, Kawabe K . Correlation between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation. Cancer 1999; 85: 1822–1827.

    Article  CAS  Google Scholar 

  19. Miyata Y, Kanda S, Sakai H, Hakariya T, Kanetake H . Relationship between changes in prostate cancer cell proliferation, apoptotic index, and expression of apoptosis-related proteins by neoadjuvant hormonal therapy and duration of such treatment. Urology 2005; 65: 1238–1243.

    Article  Google Scholar 

  20. Lu Q-L, Abel P, Foster CS, Lalani E-M . Bcl-2: role in epithelial differentiation and oncogenesis. Hum Pathol 1996; 27: 102–110.

    Article  CAS  Google Scholar 

  21. Colombel M, Symmans F, Gil S, O'Toole KM, Chopin D, Benson M et al. Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers. Am J Pathol 1993; 143: 390–400.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Raffo AJ, Perlman H, Chen MW, Day ML, Streitman JS, Buttyan R . Overexpression of Bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res 1995; 55: 4438–4445.

    CAS  PubMed  Google Scholar 

  23. Finlay CA, Hinds PW, Levine AJ . The p53 proto-oncogene can act as a suppressor of transformation. Cell 1989; 57: 1083–1093.

    Article  CAS  Google Scholar 

  24. Grossfeld GD, Olumi AF, Connolly JA, Chew K, Gibney J, Bhargava V et al. Locally recurrent prostate tumors following either radiation therapy or radical prostatectomy have changes in KI-67 labeling index, p53 and bcl-2 immunoreactivity. J Urol 1998; 159: 1437–1443.

    Article  CAS  Google Scholar 

  25. Stapleton AM, Zbell P, Kattan MW, Yang G, Wheeler TM, Scardino PT et al. Assessment of the biological markers p53, Ki-67, and apoptotic index as predictive indicators of prostate carcinoma recurrence after surgery. Cancer 1998; 82: 168–175.

    Article  CAS  Google Scholar 

  26. Lewis JS, Vollmer RT, Humphrey PA . Carcinoma extent in prostate needle biopsy tissue in the prediction of whole gland tumor volume in a screening population. Am J Clin Pathol 2002; 118: 442–450.

    Article  Google Scholar 

  27. Klotz L, Correia A, Zhang W . The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer. Prostate Cancer Prostatic Dis 2005; 8: 179–183.

    Article  CAS  Google Scholar 

  28. Pether M, Goldenberg SL . Intermittent androgen suppression. BJU Int 2004; 93: 258–261.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from Astra Zeneca GmbH, Vienna, Austria.

Author information

Authors and Affiliations

  1. Department of Urology, LKH Graz, Medical University of Graz, Graz, Austria

    H Augustin & K Pummer

  2. Institute of Pathology, General Hospital of Mistelbach, Mistelbach, Austria

    C Freibauer

  3. Department of Urology, General Hospital of Mistelbach, Mistelbach, Austria

    L Bayer & G Lunglmayr

  4. Department of Urology, General Hospital of Oberwart, Oberwart, Austria

    F Tschurlovich & W Kuber

Authors
  1. H Augustin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Freibauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Bayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Lunglmayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F Tschurlovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W Kuber
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K Pummer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Augustin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Augustin, H., Freibauer, C., Bayer, L. et al. Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression. Prostate Cancer Prostatic Dis 9, 279–283 (2006). https://doi.org/10.1038/sj.pcan.4500883

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4500883

Keywords

This article is cited by

Search

Advanced search

Quick links