title: Tumorigenic and prognostic significance of RASSF1A expression in low-grade (WHO grade 1 and grade 2) nonmuscle-invasive bladder cancer.
abstract: OBJECTIVE
  To investigate RASSF1A expression in an attempt to understand the effect of RASSF1A in low-grade, nonmuscle-invasive bladder cancer (NMIBC).
  
  
  METHODS
  A total of 101 tumor tissues and normal donor-matched adjacent tissues from patients with primary low-grade NMIBC were selected. RASSF1A expression was measured by quantitative real-time polymerase chain reaction and is expressed as the ratio between the normal tissue level and the tumor tissue level (N/T ratio). RASSF1A promoter methylation was assessed using methylation-specific polymerase chain reaction.
  
  
  RESULTS
  RASSF1A mRNA expression was significantly lower in patients with RASSF1A methylation than in those with no methylation (P = .046), and RASSF1A mRNA expression was lower in the tumor tissues than in the matched normal bladder mucosa (P < .001). The RASSF1A N/T ratio was greater in grade 2 and large tumors than in grade 1 and small tumors (P < .05 for each). Kaplan-Meier estimates revealed that the differences in the RASSF1A N/T ratio were associated with significant differences in the interval to tumor recurrence (P = .018) in low-grade NMIBC. Multivariate Cox regression analysis showed that the RASSF1A N/T ratio (hazards ratio 2.354, P = .015) was an independent predictor of recurrence.
  
  
  CONCLUSIONS
  Decreased RASSF1A expression correlates with the transition from normal mucosa to bladder cancer and has prognostic value in low-grade NMIBC.
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, South Korea.
authors.forename: Yun-Sok
authors.initials: YS
authors.lastname: Ha
authors.forename: Pildu
authors.initials: P
authors.lastname: Jeong
authors.forename: Ji Sang
authors.initials: JS
authors.lastname: Kim
authors.forename: Whi-An
authors.initials: WA
authors.lastname: Kwon
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Yung-Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D019175:DNA Methylation; D006801:Humans; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins