Racial differences in E-cadherin expression and CpG methylation in prostate cancer

4985 Introduction and objective: African-Americans males are twice as likely as Caucasians to present with advanced stage prostate cancer. The prostate cancer mortality rate in African-American men is 2-3 fold higher than in Caucasian men of similar age. E-cadherin, a protein involved in cell adhesion, has been shown to be down-regulated in prostate cancer by promoter methylation. However, it is not clear if E-cadherin promoter methylation plays a role in race-related prostate cancer. We hypothesize that differential expression and CpG methylation of E-cadherin may be a race-related factor that influences the incidence and severity of prostate cancer. Methods: To test this hypothesis, we analyzed E-cadherin promoter methylation and protein expression in 105 prostate cancer samples obtained by radical prostatectomy from 32 African-American and 73 Caucasian men. E-cadherin promotor methylation was determined by methylation-specific polymerase chain reaction (MSP) and confirmed with direct DNA sequencing. E-cadherin protein expression was determined by immunohistochemistry. Results: E-cadherin methylation was present in 49.6% of all specimens. E-cadherin methylation was present in 45% of Caucasian and 53% of African-American prostate cancer specimens. Age of diagnosis, tumor stage and grade, and PSA were similar between African-American and Caucasian patients. African-Americans with E-cadherin methylation had higher PSAs than African-Americans with no methylation (12.1 vs. 6.5 ng/mL). E-cadherin protein expression, as determined by immunohistochemistry, inversely correlated with methylation in both racial groups (p=0.002). Conclusion: E-cadherin promoter CpG methylation correlates with decreased protein expression. Among African-Americans, E-cadherin promotor methylation correlates with higher PSA levels; however, no such association was found in Caucasian patients. The results of these experiments may provide us with novel strategies for management of prostate cancer through methylation pathways.