Loss of P16 Expression and Chromosome 9p21 LOH in Predicting Outcome of Patients Affected by Superficial Bladder Cancer

Abstract

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. 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. 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. 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.