Der Urologe, Ausgabe A

, Volume 43, Issue 5, pp 573–579

Die GSTP1-CpG-Insel-Hypermethylierung als molekularer Marker des Prostatakarzinoms

  • P. J. Bastian
  • M. Nakayama
  • A. M. De Marzo
  • W. G. Nelson
Originalien

Zusammenfassung

Hintergrund

Das Prostatakarzinom (PCA) ist das häufigste Karzinom der männlichen Bevölkerung in Europa und Nordamerika. Trotz der hohen Prävalenz ist der molekulare Ablauf der Entstehung und der Progression nur teilweise bekannt. In zahlreichen Untersuchungen wurden die molekulargenetischen Alterationen in der Pathogenese des Prostatakarzinoms bearbeitet. Die CpG-Insel-Hypermethylierung des Glutathion-S-tranferase-Gens (GSTP1) ist eine dieser charakteristischen Veränderung in der Karzinogenese des Prostatakarzinoms.

Material und Methoden

Wir haben die Bedeutung der GSTP1-CpG-Insel-Hypermethylierung in der Karzinogenese des Prostatakarzinoms untersucht und auf die klinische Anwendung hin geprüft.

Ergebnisse

In den Untersuchungen konnte die GSTP1-CpG-Insel-Hypermethylierung bei mehr als 90% der Prostatakarzinome festgestellt werden. Es gelang der Nachweis in verschiedenen Körperflüssigkeiten (Blut, Urin, Ejakulat, Prostatasekret) und bei im Rahmen einer radikalen Prostatektomie entfernten Lymphknoten; eine Unterscheidung zwischen normalem Prostatagewebe, der benignen Prostatahyperplasie, Vorläuferstadien des Prostatakarzinoms und dem Prostatakarzinom ist durch die modernen, molekulargenetischen Untersuchungstechniken möglich.

Schlussfolgerungen

Mit dem Nachweis der GSTP1-CpG-Insel-Hypermethylierung steht ein molekularer Test zur Verfügung, der das Screening und die Diagnostik des Prostatakarzinoms verbessert. Ein spezifisches Methylierungsmuster des PCA könnte als molekulares Staging Aussagen über die Prognose des PCA leisten. Zur Bestätigung der vielversprechenden, aber noch experimentellen Ergebnisse sind allerdings große prospektive Studien erforderlich.

Schlüsselwörter

Prostatakarzinom CpG Insel Glutathion-S-Transferase DNA-Methylierung 

GSTP1 CpG island hypermethylation as a molecular marker in the carcinogenesis of prostate cancer

Abstract

Background

Prostate cancer is the most commonly diagnosed cancer in men in Europe and North America. Despite its high prevalence, the molecular mechanism of its underlying development and progression is poorly understood. Many studies have revealed multiple molecular alterations during prostate cancer carcinogenesis. GSTP1 CpG island hypermethylation is one of the molecular changes that occur during carcinogenesis.

Methods

We evaluated the role of GSTP1 CpG island hypermethylation in prostatic cancers and discussed its possible role as a molecular biomarker of prostate cancer.

Results

Studies haven shown that GSTP1 CpG island hypermethylation is present in about 90% of prostatic carcinomas. The DNA alteration was also detectable in body fluids such as blood, urine, ejaculate, or prostatic secretions. One study showed hypermethylation in histologically unsuspicious lymph nodes in surgical specimens in patients with biochemical PSA (prostate-specific antigen) recurrence. Additionally, it is possible to distinguish between normal prostatic tissue, benign prostatic hyperplasia, and prostate cancer.

Conclusions

The detection of GSTP1 CpG island hypermethylation serves as a molecular marker in prostate cancer screening, detection, and diagnosis. It may even provide information on prostate cancer prognosis. However, prospective trials to evaluate its predictive value are necessary.

Keywords

Prostate cancer Glutathione S-transferase CpG island DNA methylation 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • P. J. Bastian
    • 1
    • 4
  • M. Nakayama
    • 2
  • A. M. De Marzo
    • 1
    • 2
    • 3
  • W. G. Nelson
    • 1
    • 2
    • 3
  1. 1.The James Buchanan Brady Urological InstituteThe Johns Hopkins University School of MedicineBaltimore, Maryland
  2. 2.Department of PathologyThe Johns Hopkins University School of MedicineBaltimore, Maryland
  3. 3.The Sidney Kimmel Comprehensive Cancer CenterThe Johns Hopkins University School of MedicineBaltimore, Maryland
  4. 4.The James Buchanan Brady Urological Institute, The Johns Hopkins University School of MedicineBunting Blaustein Cancer Research Building, CRB 152Baltimore, MD 21231

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