Objective: To study the mechanism of invasion and metastasis in early nasopharyngeal carcinoma (NPC) in relation to E-cadherin promoter methylation and mutation in exon 3 of beta-catenin.
Methods: Methylation of E-cadherin promoter, mutation in exon 3 of beta-catenin and differential expression of beta-catenin in the primary lesion of 21 NPC and the metastatic lymph node of 21 NPC were investigated by DNA Methylation-Specific PCR, direct sequencing and immunohistochemical method.
Results: Methylation on E-cadherin promoter was showed in 23.8% (5/21) primary lesions and 61.9% (13/21) metastatic lymph nodes (P < 0.01). Mutation in exon 3 of beta-catenin was showed in 3 of 42 tissues: codon 37 (TCT-->GCT), codon 41 (ACC-->GCC) and codon 47 (AGT-->ACT). However, there was no relation between these mutations and invasion or metastasis (P > 0.05). High beta-catenin expression on the membrane without nuclear expression was observed in 42 tissues (P > 0.05).
Conclusion: 1. In NPC, methylation of promoter is a major cause of down-regulation of E-cadherin which may finally lead to detachment and metastasis of neoplastic cells, 2. Mutation in exon 3 of beta-catenin is a rare event in NPC. It may be an early event in the carcinogenesis of NPC but have no significant role in invasion and metastasis and 3. High expression of beta-catenin, as one of NPC characteristics, is not a key factor for invasion or metastasis.