Evaluation of methylation pattern in promoter region of E-cadherin gene and its relation to tumor grade and stage in breast cancer

Abstract

The epithelial cadherin gene (CDH1) has been identified as a tumor suppressor gene located within the 16q22.1 region. The CDH1 gene encodes a transmembrane glycoprotein involved in cell to cell adhesion and loss of CDH1 expression contributes to increased proliferation, invasion and metastasis in breast carcinoma. No mutation in CDH1 have been identified in invasive ductal carcinoma (IDC), suggesting that, other inactivation mechanisms are responsible for IDC oncogenesis. In order to analyze the role of promoter methylation in CDH1 gene inactivation in breast cancer, the CpG methylation status of Ecadherin promoter region by bisulfite sequencing PCR (BSP) was investigated. 10 CpG sites [nucleotide (nt) 863, 865, 873, 879, 887, 892, 901, 918, 920 and 940] in the promoter region were screened for methylation. The CDH1 methylation was detected in 94% (47 to 50) of breast tumors which was associated with higher tumor grade (p = 0.035), tumor stage (p = 0.000) and tumor metastasis (p = 0.000). There was also a significant correlation between tumor stage, grade and metastatic status with sites of methylation (p = 0.000). The data indicate that CDH1 promoter methylation might be a potential mechanism for epigenetic silencing of CDH1 in primary breast cancer suggesting a valuable molecular marker for detection of breast cancer progression.

Key words: Breast cancer, E-cadherin, methylation pattern, tumor stage, tumor grade.