title: Loss of P16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer.
abstract: OBJECTIVE
  To evaluate the prognostic role of p16 expression and loss of heterozygosity (LOH) on chromosome 9p21 in patients affected by low-grade (G1-G2) urothelial bladder cancer.
  
  
  METHODS
  Fifty-six consecutive patients with diagnosis of urothelial bladder cancer were enrolled in this prospective study. LOH analysis was performed on a blood/tumor pair sample of each patient, by using polymerase chain reaction analysis. The D9S171 (9p21) locus on chromosome 9 was investigated. All tumors were stained immunohistochemically for p16. Data from p16 and LOH analyses were compared with follow-up data to evaluate the prognostic role of these molecular markers.
  
  
  RESULTS
  Loss of p16 expression was found in 33 patients (58.9%) and was significantly associated with the reduced recurrence-free probability (P < 0.0001). No correlations were reported with stage (P = 0.162) or grade (P = 0.051). Forty-three patients (76.7%) showed LOH on chromosome 9p21 (D9S171). A significant association was observed between loss of p16 expression and LOH on chromosome 9p21 (P = 0.005). The Kaplan-Meier curves showed a significant correlation between recurrence-free status and p16 expression (P = 0.0001). By multivariate analysis, p16 expression (P = 0.002) and number of lesions (P = 0.002) were identified as independent tumor recurrence factors.
  
  
  CONCLUSIONS
  Our study highlights the prognostic role of p16 in predicting the recurrence-free probability in patients affected by low-grade urothelial bladder and highlights the fact that this method could be used in everyday urologic clinical practice to better characterize the natural history of urothelial bladder carcinomas.
authors.affiliation: Department of Urology, University of Florence, Italy, Florence, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bartoletti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cai
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Lucia
authors.initials: L
authors.lastname: Roberta Girardi
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Dal Canto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D019459:Urothelium
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers