Aberrant methylation of E-cadherin promoter in salivary adenoid cystic carcinoma

Objectives: Loss of E-cadherin(E-cad) is correlated with tumor development, invasion and metastasis and is associated with aberrant promoter methylation. The current study is to clarify the role of methylation status of E-cad in tumorgenesis and progression of salivary adenoid cystic carcinoma(ACC).Methods: Genomic DNA was obtained from tissue sections of 60 cases of primary ACC, using microdissection method. Methylation status of the E-cad was determined by methylation-specific PCR. The association between methylation status and the patients' clinicopathologic characteristics were assessed. Methylation status of the gene in normal salivary gland tissues was also examined. Results: DNA methylation of the E-cad promoter was detected in 34 of 60 tumors(57%). The E-cad promoter frequency was higher in high-grade tumors than in low-grade tumors(P=0.0063) and in tumors with perineural/perivascular invasion(P=0.0243), but it had no correlation with TNM stage and tumor metastasis. The methylation status in normal salivary gland tissues was much lower(3/50,6%).Conclusions: The results indicate that the E-cad gene promoter is frequently methylated in ACC. The frequent E-Cad methylation in ACC, also in high-grade tumors and in tumors with perineural/perivascular invasion, suggests a role of the gene in the tumor development, progression and invasion of ACC.