Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer.
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.
Kollermann
Jens
J
Urologische Klinik, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. J.Koellermann@t-online.de
Kempkensteffen
Carsten
C
Helpap
Burkhard
B
Schrader
Mark
M
Krause
Hans
H
Muller
Markus
M
Miller
Kurt
K
Schostak
Martin
M
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
D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi