Inverse association of p16INK4a and p14ARF methylation of the CDKN2a locus in different Gleason scores of prostate cancer

Abstract

Promoter hypermethylation is an important epigenetic mechanism in the regulation of several key modulators of prostate carcinoma progression. Recent studies suggest that the polycomb-group (PcG) protein BMI1 may have an impact on epigenetic regulation of several targets, including the CDKN2a locus. In this study, we investigated the association of BMI1 expression, promoter methylation of CDKN2a (p16(INK4a) and p14(ARF)) and TMS1 with pathological variables (Gleason score, TNM stage, perineural invasion) in prostate cancer (PCa). Methylation of p16(INK4a) and p14(ARF) revealed an inverse association with Gleason score 7b and Gleason score 6. No significant association could be demonstrated for BMI1 -overexpression and promoter methylation of p16(INK4a), p14(ARF) and TMS1 as well as pT category. Our data suggest that the CDKN2a locus is a switch in PCa with methylation of p16(INK4a) being a marker for more aggressive tumours of Gleason score 7b, but no association with BMI overexpression was observed.