Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

Abstract BACKGROUND DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer‐specific methylation in prostate cancer. METHODS Direct sequencing of bisulfite‐treated genomic DNA, conventional methylation‐specific PCR (MSP), real‐time quantitative methylation‐specific PCR, immunohistochemistry, colony formation assay, and statistical analysis. RESULTS We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non‐neoplastic prostate (BPH) tissues by direct sequencing of bisulfite‐treated genomic DNA and conventional methylation‐specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) ( P = 0.001) and Gleason score ( P = 0.018) in primary prostate carcinoma. CONCLUSIONS Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer. Prostate 68: 418–426, 2008. © 2008 Wiley‐Liss, Inc.