E-Cadherin Promoter Hypermethylation in Sporadic Colorectal Cancer

Aims: E-cadherin belongs to a family of calcium-dependent adhesion molecules that mediate intercellular contacts critical to morphogenesis and the maintenance of cellular architecture. Previous studies have implicated the loss of E-cadherin in tumour progression, invasion and metastasis. Promoter hypermethylation has been associated with transcriptional silencing of several genes, including E-cadherin, in various forms of cancer.

Method: We investigated the extent of E-cadherin promoter-hypermethylation in a series of 73 sporadic colorectal cancers, and examined correlations with patients' clinicopathological features and additional molecular features. Using DNA extracted from snap-frozen paired tumour and normal tissue, the methylation status of the E-cadherin promoter was investigated in each case with methylation-specific PCR. We have previously established the promoter hypermethylation status of hMLH1 and MGMT, as well as the microsatellite instability status, in these tumours.

Results: E-cadherin promoter hypermethylation was detected in 67% (48/73) of cases. This was associated with late Dukes stage, although this did not reach statistical significance (p=0.072, chi-square test for trend). No additional clinicopathological associations were seen to be statistically significant. A statistically significant relationship was observed between E-cadherin promoter hypermethylation and absence of MLH1 promoter hypermethylation (p=0.021, Fisher's Exact Test).

Conclusion: This association may constitute further evidence of distinct hypermethylation-associated pathways in CRC.