Quantitative promoter hypermethylation profiles of ductal carcinoma in situ in north american and korean women: Potential applications for diagnosis

To investigate the diagnostic potential of DNA methylation-based markers in tissue samples of DCIS, we examined the prevalence and extent of methylation in breast ductal carcinoma in situ (DCIS) samples from North American and Korean women. Quantitative multiplex-methylation specific PCR (QM-MSP) of ten genes was performed. The methylation level of APC1, Cyclin D2, HIN-1, RASSF1A and Twist singly, and cumulative methylation of all ten genes was significantly higher in DCIS compared to normal tissues for both groups. A three-gene panel (APC1, HIN-1 and RASSF1A) QM-MSP distinguished between DCIS and normal breast tissues with a sensitivity of 94 to 96% and a specificity of 81 to 87%. Methylation levels of these three genes in DCIS were higher than those of hyperplasia or adjacent normal appearing tissues in Korean women. Comparing North American and Korean DCIS, statistically significant differences in methylation levels were found for CDH1, ERα and RAR-β. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERα. Our study demonstrated that methylation profiles of DCIS between North American and Korean women were similar. Methylation status of a panel of genes measured in a quantitative manner accurately discriminated between normal and DCIS tissues of both groups. For both North American and Korean women, QM-MSP analysis of a key panel of genes may be useful as an ancillary tool for DCIS detection in breast tissues.