Multigene methylation in serum of sporadic Chinese female breast cancer patients as a prognostic biomarker.

OBJECTIVE: DNA methylation is a common molecular alteration in human neoplasia and can be detected easily in the bloodstream of patients. Here, we investigated whether DNA methylation in sera is of prognostic significance in breast cancer patients.
METHODS: Methylation status of BRCA1, p16 and 14-3-3sigma was examined by methylation-specific PCR assay in the sera of sporadic breast cancer patients and healthy serum controls.
RESULTS: The panel gene methylation frequencies were 29% of sporadic breast cancers for p16, 32% for BRCA1 and 82% for 14-3-3sigma; all were significantly associated with grades and estrogen receptor status. Only p16 methylation was associated with histological type. p16 and BRCA1 methylation were associated with progesterone receptor status, while 14-3-3sigma was significantly associated with lymph node metastases. Seventy percent of patients with p16 methylation showed elevated serum CEA levels; of the breast cancer patients with BRCA1 methylation, 75.8% showed elevated serum CEA levels and 69.7% showed elevated serum CA15.3 levels. When analyzing all investigated patients, multivariate analysis showed methylated BRCA1 and/or p16 serum DNA to be independently associated with poor outcome, with a relative risk of death of 6.0.
CONCLUSIONS: Epigenetic markers in sera, especially BRCA1/p16, may be more promising targets for the diagnosis of sporadic breast cancer than previous prognostic markers. Copyright 2008 S. Karger AG, Basel.