Quantitative promoter hypermethylation profiles of ductal carcinoma in situ in North American and Korean women: Potential applications for diagnosis

Abstract

To investigate the diagnostic potential of DNA methylation-based markers in tissuesamples of DCIS, we examined the prevalence and extent of methylation in breastductal carcinoma in situ (DCIS) samples from North American and Korean women.Quantitative multiplex-methylation specific PCR (QM-MSP) of ten genes wasperformed. The methylation level of APC1, Cyclin D2, HIN-1, RASSF1A, and Twistsingly, and cumulative methylation of all ten genes was significantly higher in DCIScompared to normal tissues for both groups. A three-gene panel (APC1, HIN-1, andRASSF1A), QM-MSP distinguished between DCIS and normal breast tissues with asensitivity of 94 to 96% and a specificity of 81 to 87 %. Methylation levels of thesethree genes in DCIS were higher than those of hyperplasia or adjacent normal appearingtissues in Korean women. Comparing North American and Korean DCIS, statisticallysignificant differences in methylation levels were found for CDH1, ER α and RAR- β.Quantification of gene methylation combined with immunohistochemistry in a smallsubset of tumors suggested that methylation may precede loss of protein expression forER-α. Our study demonstrated that methylation profiles of DCIS between NorthAmerican and Korean women were similar. Methylation status of a panel of genesmeasured in a quantitative manner accurately discriminated between normal and DCIStissues of both groups. For both North American and Korean women, QM-MSPanalysis of a key panel of genes may be useful as an ancillary tool for DCIS detection inbreast tissues.