Modest promoter methylation of E-cadherin gene in sporadic colorectal cancers: a quantitative analysis.

Although E-cadherin expression is frequently reduced in colorectal cancers (CRCs), this does not appear to be due to gene mutation or allele loss. We investigated the hypothesis that promoter methylation could be responsible for suppression of E-cadherin expression in 142 pairs of sporadic CRCs and respective normal mucosae. E-cadherin expression was examined by Western blot. E-cadherin methylation at two promoter regions was quantitatively measured by methylation specific real time PCR (MethyLight). We found that E-cadherin protein levels were significantly lower in CRCs, even in Dukes' A tumors, compared to normal mucosae. Decreased E-cadherin protein expression in CRCs was an independent poor prognostic factor in multivariate disease-free survival analysis. However, the extent of DNA methylation was extremely modest at both regions of the E-cadherin promoter. There was no correlation between DNA methylation and E-cadherin protein levels in either tumors or matched normal tissues. These findings suggested that suppression of E-cadherin expression in CRCs is a significant event and is possibly involved in both carcinoma development and progression. However, our data did not support a crucial role of promoter methylation of the E-cadherin gene in the remarkable downregulation of E-cadherin expression in CRCs. Methylated E-cadherin gene as a CRC biomarker therefore needs further validation.