Aberrant methylation of the estrogen receptor and E-cadherin 5 ' CpG islands increases with malignant progression in human breast cancer

Loss of expression for both the estrogen receptor-alpha and E-cadherin gene s has been linked to disease progression in human ductal breast carcinomas and has been associated with aberrant 5' CpG island methylation. To assess when, during malignant progression, such methylation begins and whether suc h methylation increases with advancing disease, we have surveyed 111 ductal carcinomas of the breast for aberrant methylation of the estrogen receptor -alpha and E-cadherin 5' CpG islands, Hyper-methylation of either CpG islan d was evident prior to invasion in similar to 30% of ductal carcinoma in si tu lesions and increased significantly to nearly 60% in metastatic lesions. Coincident methylation of both CpG islands also increased significantly fr om similar to 20% in ductal carcinoma irt situ to nearly 50% in metastatic lesions. Furthermore, in all cases, the pattern of methylation displayed su bstantial heterogeneity, reflecting the a ell-established, heterogeneous lo ss of expression for these genes in ductal carcinomas of the breast.