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Molecular Oncology, Markers, Clinical Correlates |
Departments of Anatomical and Cellular Pathology [M. W. Y. C., J. H. M. T., K. W. L., T. L. L., F. M. M. L., K. F. T.], Surgery [L. W. C., H. Y. C., W. S. W., P. S. F. C.], and Chemical Pathology [N. L. S. T.], The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People’s Republic of China
Purpose: We aimed to investigate the methylation pattern in bladder cancer and assess the diagnostic potential of such epigenetic changes in urine.
Experimental Design: The methylation status of 7 genes (RARß, DAPK, E-cadherin, p16, p15, GSTP1, and MGMT) in 98 cases of bladder transitional cell carcinoma and 4 cases of carcinoma in situ was analyzed by methylation-specific PCR. Twenty-two cases had paired voided urine samples for analysis.
Results: In transitional cell carcinoma tumor tissues, aberrant methylation was frequently detected in RARß (87.8%), DAPK (58.2%), E-cadherin (63.3%), and p16 (26.5%), whereas methylation of p15 (13.3%), GSTP1 (5.1%), and MGMT (5.1%) is not common. No association between methylation status and grading or muscle invasiveness was demonstrated. In 22 paired voided urine samples of bladder cancer, methylation of DAPK, RARß, E-cadherin, and p16 could be detected in 45.5%, 68.2%, 59.1%, and 13.6% of the cases, respectively. The sensitivity of methylation analysis (90.9%) was higher than that of urine cytology (45.5%) for cancer detection. Methylation of RARß (50%), DAPK (75%), and E-cadherin (50%) was also detected in carcinoma in situ. In 7 normal urothelium samples and 17 normal urine controls, no aberrant methylation was detected except for RARß methylation in 3 normal urothelium samples (42.9%) and 4 normal urine samples (23.5%), respectively.
Conclusions: Our results demonstrated a distinct methylation pattern in bladder cancer with frequent methylation of RARß, DAPK, E-cadherin, and p16. Detection of gene methylation in routine voided urine using selected markers appeared to be more sensitive than conventional urine cytology.
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