DNA methylation of the PITX2 gene promoter region is a strong independent prognostic marker of biochemical recurrence in patients with prostate cancer after radical prostatectomy.
OBJECTIVE
Approximately 35% of patients with prostate cancer who undergo radical prostatectomy experience prostate specific antigen recurrence within 10 years of surgery. Current prognostic indicators cannot sufficiently detect who is at risk for biochemical recurrence. We evaluated DNA methylation markers for prostate cancer prognosis.


METHODS
We assessed the DNA methylation of 6 marker candidates that were identified in previous studies. Formalin fixed, paraffin embedded tissue sections from a cohort of 605 patients who underwent radical prostatectomy were analyzed using real-time polymerase chain reaction assays. Using a Cox proportional hazard model we determined which markers were significant predictors of biochemical recurrence.


RESULTS
ABHD9, Chr3-EST, GPR7, HIST2H2BF and PITX2 were significantly associated with biochemical recurrence. PITX2 methylation was the strongest predictor of biochemical recurrence, providing additional prognostic information to established clinical factors in patients treated with radical prostatectomy and especially in patients at intermediate risk (Gleason 7). Patients with greater than median PITX2 methylation in the tumors were 4 times more likely to experience biochemical recurrence within 8 years after surgery than patients with less than average methylation.


CONCLUSIONS
The prognostic information provided by PITX2 methylation adds significantly to currently used clinical variables such as Gleason grade and stage. Therefore, it could contribute to better counseling in patients with prostate cancer.
Weiss
Gunter
G
Epigenomics, A. G., Charite-Universitätsmedizin Berlin, Berlin, Germany.
Cottrell
Susan
S
Distler
Jürgen
J
Schatz
Philipp
P
Kristiansen
Glen
G
Ittmann
Michael
M
Haefliger
Carolina
C
Lesche
Ralf
R
Hartmann
Arndt
A
Corman
John
J
Wheeler
Thomas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000601:surgery*; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2