B9
Promoter hypermethylation in urothelial carcinomas of young and elderly patients: a comparative study
Helen C Owen1, Arndt Hartmann2, S Larré1, Freddie C Hamdy1, James W Catto1
1Institute for Cancer Studies and Academic Unit of Urology, University of Sheffield, Sheffield, UK, 2Department of Pathology, University of Erlangen, Erlangen, Germany
Background
Aberrant DNA methylation is an important event in carcinogenesis that increases with age in non-malignant tissues. This relationship is thought to partially explain the increase in malignancy seen within the elderly. We have previously shown that promoter hypermethylation can be an accurate predictor of bladder cancer (BC) progression. BC is commonest in the elderly (median age 70) and little is known about these tumours in young patients. Recently, it has been shown that genomic aberrations are rare in urothelial tumours of young patients, a finding that has also been reported in inverted papillomas of the urinary tract (IP). In this study, we compare the methylation status of a panel of genes known to be associated with adverse clinical outcome in urothelial cancer samples from young and elderly patients, and also those diagnosed with IP.
Method
Quantitative methylation-specific PCR was carried out in urothelial tumours from 14 patients aged under 19 years, 19 patients aged under 45 years and 31 patients over 60 years (‘elderly’). Results were compared to methylation status in IP tumours from a total of 35 patients (median age 61).
Results
Promoter methylation occurred frequently in samples from elderly patients, and patients under 45, but was reduced in samples from younger patients and from patients with IP when measuring methylation levels for EDNRB, WIF1, APC and Bcl2 (p<0.05). Promoter methylation of TNFRS25 and MGMT was unchanged between patient groups.
Conclusion
These results suggest that promoter hypermethylation is not an important factor in tumour progression for young patients, or patients with IP.
