Skip to main content

Advertisement

Log in

GSTP1 CpG island hypermethylation for DNA-based detection of occult tumor cells in surgical margins after radical prostatectomy

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Objective

The risk of local recurrence after radical prostatectomy (RP) is considerably dependent on local tumor stage. To improve local staging, the aim of this study was to assess the feasibility of quantitative methylation-specific PCR (Q-MSP) for the identification of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa) cells in the prostatic fossa after RP.

Methods

A total of 39 consecutive patients with clinically organ-confined PCa underwent RP. After gland excision, biopsies were obtained from eight defined areas of the prostatic fossa and bisected for both histopathological and molecular analyses. Results were related to clinicopathological data including tumor stage, Gleason score, prostate-specific antigen (PSA), and biochemical recurrence.

Results

Of 39 patients, 11 with PCa had at least one positive molecular margin status indicated by GSTP1 methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22 (27.3%) with advanced (≥pT3 and/or pN+) PCa. GSTP1 methylation in surgical margins strongly correlated with histopathological R-status (P = 0.022) and preoperative PSA (P = 0.01) whereas no association with tumor stage (pT2 vs pT3), grade (Gleason score <7 vs ≥7), and lymph node status was found. No patient experienced biochemical relapse.

Conclusions

GSTP1 hypermethylation detected by Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of occult tumor cells in surgical margins. However, the limited number of patients and the short-term follow-up does not allow definite conclusions on the prognostic value of GSTP1 in surgical margins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Kattan MW, Eastham JA, Stapleton AM, Wheeler TM, Scardino PT (1998) A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 90:766–771

    Article  PubMed  CAS  Google Scholar 

  2. Swindle P, Eastham JA, Ohori M, Kattan MW, Wheeler T, Maru N, Slawin K, Scardino PT (2008) Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol 179:47–51

    Article  Google Scholar 

  3. Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinical localized prostate cancer. J Urol 169:517–523

    Article  PubMed  Google Scholar 

  4. Bolla M, Poppel H, Collette L, Cangh P, Vekemans K, Da Pozzo L, Reijke TM, Verbaeys A, Bosset JF, Velthoven R, Maréchal JM, Scalliet P, Haustermans K, Piérart M (2005) Postoperative radiotherapy after radical prostatectomy: a randomised controlled trail (EORTC trail 22911). Lancet 366:572–578

    Article  PubMed  Google Scholar 

  5. Nelson WG, De Marzo AM, Isaacs WB (2003) Prostate cancer. N Engl J Med 349:366–381

    Article  PubMed  CAS  Google Scholar 

  6. Goessl C, Müller M, Heicappell R, Krause H, Miller K (2001) DNA-based detection of prostate cancer in blood, urine, and ejaculates. Ann NY Acad Sci 945:51–58

    Article  PubMed  CAS  Google Scholar 

  7. Köllermann J, Müller M, Goessl C, Krause H, Helpap B, Pantel K, Miller K (2003) Methylation-specific PCR for DNA-based detection of occult tumor cells in lymph nodes of prostate cancer patients. Eur Urol 44:533–538

    Article  PubMed  Google Scholar 

  8. Bastian PJ, Palapattu GS, Lin X, Yegnasubramanian S, Mangold LA, Trock B, Eisenberger MA, Partin AW, Nelson WG (2005) Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res 11(11)

  9. Nakayama M, Gonzalgo ML, Yegnasubramanian S, Lin X, De Marzo AM, Nelson WG (2004) GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer. J Cell Biochem 91:540–552

    Article  PubMed  CAS  Google Scholar 

  10. Hanson JA, Gillespie JW, Grover A, Tangrea MA, Chuaqui RF, Emmert-Buck MR, Tangrea JA, Libutti SK, Linehan WM, Woodson KG (2006) Gene promoter methylation in prostate tumor-associated stromal cells. J Natl Cancer Inst 98(4):255–261

    Article  PubMed  CAS  Google Scholar 

  11. McNeal JE (1969) Origin and development of carcinoma of the prostate. Cancer 23:24

    Article  PubMed  CAS  Google Scholar 

  12. Chen ME, Johnston DA, Tang K, Babaian RJ, Troncoso P (2000) Detailed mapping of prostate carcinoma foci: biopsy strategy implications. Cancer 89(8):1800–1809

    Article  PubMed  CAS  Google Scholar 

  13. Jeronimo C, Usadel H, Henrique R, Oliveira J, Lopes C, Nelson WG, Sidransky D (2001) Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma. J Natl Cancer Inst 93:1747–1752

    Article  PubMed  CAS  Google Scholar 

  14. Straub B, Müller M, Krause H, Goessl C, Schrader M, Heicappell R, Miller K (2001) Reverse transcriptase-polymerase chain reaction for prostate-specific antigen in the molecular staging of pelvic surgical margins after radical prostatectomy. Urol 57:1006–1011

    Article  PubMed  CAS  Google Scholar 

  15. Theodorescu D, Frierson HF, Sikes RA (1999) Molecular determination of surgical margins using fossa biopsies at radical prostatectomy. J Urol 161:1442–1448

    Article  PubMed  CAS  Google Scholar 

  16. Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG, De Marzo AM (2003) Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplasitc epithelium of the prostate: a detailed study using laser-capture microdissection. Am J Pathol 163:923–933

    Article  PubMed  CAS  Google Scholar 

  17. Bastian PJ, Yegnasubramanian S, Palapattu GS, Rogers CG, Lin X, De Marzo AM, Nelson WG (2004) Molecular biomarker in prostate cancer: the role of CpG island hypermethylation. Eur Urol 46:698–708

    Article  PubMed  CAS  Google Scholar 

  18. Harden SV, Sanderson H, Goodman SN, Partin AA, Walsh PC, Epstein JI, Sidransky D (2003) Quantitative GSTP1 methylation and the detection of prostate adenocarcinoma in sextant biopsies. J Natl Cancer Inst 95:1634–1637

    Article  PubMed  CAS  Google Scholar 

  19. Henrique R, Jeronimo C (2004) Molecular detection of prostate cancer: a role for GSTP1 hypermethylation. Eur Urol 46:660–669

    Article  PubMed  CAS  Google Scholar 

  20. Bastian PJ, Ellinger J, Heukamp LC, Kahl P, Müller SC, von Rücker A (2007) Prognostic value of CpG island hypermethylation at PTGS2, RAR-beta, EDNRB and other gene loci in patients undergoing radical prostatectomy. Eur Urol 51:665–674

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are very grateful to the skillful technical assistance of Mrs. Waltraud Jekabsons.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Florian Jentzmik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jentzmik, F., Krause, H., Reichelt, U. et al. GSTP1 CpG island hypermethylation for DNA-based detection of occult tumor cells in surgical margins after radical prostatectomy. World J Urol 30, 541–546 (2012). https://doi.org/10.1007/s00345-011-0764-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-011-0764-2

Keywords

Navigation