title: Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer.
abstract: BACKGROUND
  In spite of excellent cure rates for prostate cancer patients with favorable tumor characteristics, patients with unfavorable characteristics after radical prostatectomy are still at a significantly increased risk of tumor progression. Early adjuvant hormonal therapy (AHT) has been shown to be of prognostic benefit in these patients. Unfortunately initiation and duration of early AHT in the individual patient is based on statistic data. PSA, as the standard prostate marker is neither able to reliably indicate minimal residual tumor disease in the early postoperative phase, nor can it be used for therapy monitoring due to the suppressive effect of hormonal therapy on PSA production. Promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1-HM) has been shown to be the most common DNA alteration of primary prostatic carcinoma which, when used as a marker, is supposed to be able to overcome some of the disadvantages of PSA. However until now information on the impact of hormonal therapy on the detection of GSTP1-HM is lacking. The purpose of our study was to assess the impact of endocrine therapy on the detection of GSTP1-HM by methylation-specific PCR (MSP) in prostate cancer.
  
  
  METHODS
  Paraffin embedded tumor samples from the radical prostatectomy (RP) specimens from 15 patients after hormonal therapy (HT) (mean 8 months) were assessed by MSP. In 8 of the patients the GSTP-1 status of the tumors before HT was assessed on the corresponding initial diagnostic biopsies.
  
  
  RESULTS
  Following HT MSP showed GSTP1-HM in 13/15 of the RP specimens. In two patients analysis of the RP specimens failed to show GSTP1-HM. All initial tumor samples (8/8 biopsy specimens) showed GSTP1-HM, including both patients negative for GSTP1 HM in the corresponding RP specimen.
  
  
  CONCLUSIONS
  In most cases hormonal therapy appears to not alter GSTP1 HM detection. However the change from a positive to a negative GSTP1 HM status in a subset of the patients may point to an, at least partial androgen dependency. Further studies on a larger cohort of patients are necessary to assess its frequency and the exact hormonal interactions.
authors.affiliation: Urologische Klinik, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. J.Koellermann@t-online.de
authors.forename: Jens
authors.initials: J
authors.lastname: Kollermann
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Burkhard
authors.initials: B
authors.lastname: Helpap
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Markus
authors.initials: M
authors.lastname: Muller
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D019175:DNA Methylation / Q000187:drug effects*; D016903:Drug Monitoring / Q000379:methods; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi