GSTP1 promoter methylation is associated with recurrence in early stage prostate cancer.
OBJECTIVE
Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.


METHODS
We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant.


RESULTS
The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05).


CONCLUSIONS
Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Leonel
L
Maldonado
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Mariana
M
Brait
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Myriam
M
Loyo
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Lauren
L
Sullenberger
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kevin
K
Wang
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Sarah B
SB
Peskoe
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Eli
E
Rosenbaum
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Roslyn
R
Howard
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Antoun
A
Toubaji
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Roula
R
Albadine
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
George J
GJ
Netto
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Mohammad O
MO
Hoque
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Elizabeth A
EA
Platz
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. Electronic address: dsidrans@jhmi.edu.
David
D
Sidransky
D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D012189:Retrospective Studies
D004273:DNA, Neoplasm; D051549:Glutathione S-Transferase pi
biological markers; glutathione S-transferase pi; local; methylation; neoplasm recurrence; prostatic neoplasms