Assessing the Use of p16 Promoter GeneMethylation in Serum for Detectionof Bladder Cancer

Objective: This study was undertaken to investigate whether hypermethylation in p16 gene promoter could serve as plasma biomarker of bladder cancer. Methods and Patients: We examined the p16 status using methylation-specific PCR in 86 cancer patients and 49 controls (31 healthy people and 18 patients with benign urological diseases). Results: The p16 methylation was found in 22% of the serum samples and in 26% of the bladder cancer biopsies; one of them with carcinoma in situ. The presence of hypermethylated p16 in serum seems to be a product from tumour cells because a strong statistical association was found between both matched DNA signals (p < 0:0001). Using the control group, the presence of methylated p16 in the serum of individuals with suspicion of bladder cancer was found to be associated with the tumour presence (p 1⁄4 0:0009). Aberrant p16 methylation was also observed in one non-cancer patient, which is undergoing further assessment. Conclusions: According with our results, methylation of p16 promoter may be involved in the bladder cancer genesis and the presence of p16 methylated in serum of these patients could be useful in the cancer diagnosis with values of sensitivity, specificity and positive predictive value of 0.226, 0.950 and 0.98, respectively. These figures support the use of methylated p16 as a new class of tumour marker in bladder cancer. # 2002 Elsevier Science B.V. All rights reserved.