Evaluation of promoter hypermethylation detection in serum as a diagnostic tool for breast carcinoma in Korean women

Objective. We have noted that quantitative multiplex-methylation specific PCR (QM-MSP) analysis of a key panel of genes may be useful as an ancillary tool for ductal carcinoma in situ (DCIS) detection in breast tissue. In this study, we investigated aberrant promoter hypermethylation of four genes as a means to detect epigenetic alterations specific to breast carcinoma in the serum of patients with DCIS and invasive ductal carcinoma (IDC). Methods. Two hundred forty-three serum samples from 89 patients with IDC, 30 patients with DCIS, and 125 age-matched healthy controls were examined. After DNA extraction and sodium bisulfite treatment, QM-MSP was performed for HIN-1, RASSF1A, RAR-β, and Twist. Results. Overall significant differences in methylation levels were observed for HIN-1 (p=0.006), RAR-β (p<0.001), RASSF1A (p=0.004), and Twist (p<0.001). All four genes showed significantly higher methylation frequencies in DCIS or IDC than in control subjects (p<0.001 for all comparisons). However, methylation frequencies were not significantly different between DCIS and IDC. In receiver-operating characteristic analysis, the two-gene combination (RAR-β/RASSF1A) showed the best performance in distinguishing DCIS/IDC from control samples. The estimated specificity of this two-gene panel for detecting DCIS/IDC was 88.8%, and its sensitivity was 94.1%. Conclusions. The quantitative detection of aberrant DNA methylation in serum samples may be a promising high throughput approach for the diagnosis of breast cancer including DCIS.