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DOI: 10.1055/s-2005-922884
Loss of E-cadherin expression in colorectal cancer
Aims: E-cadherin dysfunction is proposed to contribute to cancer progression, facilitating proliferation, invasion, and possibly metastasis. Loss of E-cadherin expression has been described secondary to somatic mutation and promoter hypermethylation in various cancers. This study sought to examine the significance of E-cadherin expression in an unselected series of colorectal cancers.
Methods: We examined E-cadherin protein expression by immunohistochemistry in a series of 66 sporadic colorectal cancers. Well-defined membranous staining was scored semi-quantitatively on quadruplicate tissue microarray (TMA) cores for each case. Correlations with patient clinicopathological features and additional molecular features were assessed. We have previously established the E-cadherin gene promoter hypermethylation status of this group by methylation-specific PCR (MSP).
Results: Loss of E-cadherin expression correlated with poor differentiation (p=0.05) and the presence of distant metastasis (p=0.02). No additional statistically significant clinicopathological associations were noted. A highly statistically significant relationship was evident between loss of E-cadherin expression and promoter hypermethylation (p<0.001). E-cadherin promoter hypermethylation itself was also associated with later disease stage.
Conclusions: Loss of E-cadherin protein expression in colorectal cancer is associated with more advanced disease. This study suggests that the mechanism underlying this loss of E-cadherin expression in advanced colorectal cancer is principally promoter hypermethylation.