title: Prognostic value of RASSF1 promoter methylation in prostate cancer.
abstract: OBJECTIVE
  Patients with prostate cancer who have biochemical recurrence after curative therapy are at higher risk for distant metastasis and cancer specific death. Assessment of aberrant DNA methylation in urine might complement currently used clinical prognostic factors and serve as a noninvasive tool for early prediction of biochemical recurrence after radical prostatectomy.
  
  
  METHODS
  Promoter methylation of 7 genes was evaluated by methylation sensitive polymerase chain reaction in 149 prostate cancer tissues, 37 noncancerous prostate tissues and 17 benign prostatic hyperplasia samples. Quantitative polymerase chain reaction was used for DNA methylation analysis of the urine of 253 patients with prostate cancer and 32 with benign prostatic hyperplasia.
  
  
  RESULTS
  In prostate cancer tissue the most frequently methylated genes were RASSF1, GSTP1 and RARB, which combined were positively identified in 85% of cases. These genes were also methylated in the urine of 60% of patients with prostate cancer. RASSF1 was methylated in 45% of prostate cancer urine samples with methylation intensity significantly higher in prostate cancer than in benign prostatic hyperplasia cases (p = 0.018). In a univariate model RASSF1 methylation and the total number of methylated genes in prostate cancer tissue were predictive of time to biochemical recurrence (p = 0.019 and 0.043, respectively). On multivariate analysis RASSF1 methylation together with pathological stage was the most significant predictor of biochemical recurrence in patients with Gleason score 6 tumors when analyzed in tissue and urine (p ≤0.001).
  
  
  CONCLUSIONS
  Hypermethylation of RASSF1 in cancerous tissue and urine from patients with prostate cancer correlated with biochemical recurrence after radical prostatectomy. The prognostic potential of this biomarker deserves further investigation.
authors: Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors: Kristina
authors: K
authors: Daniunaite
authors: Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania. Electronic address: sonata.jarmalaite@gf.vu.lt.
authors: Sonata
authors: S
authors: Jarmalaite
authors: Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors: Neringa
authors: N
authors: Kalinauskaite
authors: Faculty of Medicine, Vilnius University, Vilnius, Lithuania; National Centre of Pathology, Vilnius, Lithuania.
authors: Donatas
authors: D
authors: Petroska
authors: Faculty of Medicine, Vilnius University, Vilnius, Lithuania; National Centre of Pathology, Vilnius, Lithuania.
authors: Arvydas
authors: A
authors: Laurinavicius
authors: Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors: Juozas R
authors: JR
authors: Lazutka
authors: Faculty of Medicine, Vilnius University, Vilnius, Lithuania; Urology Centre, Vilnius University, Vilnius, Lithuania.
authors: Feliksas
authors: F
authors: Jankevicius
mesh_terms: D019175:DNA Methylation; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins
keywords: DNA methylation; biological markers; prostate; prostatic neoplasms; recurrence