Promoter Hypermethylation of DNA Repair Gene MGMT in Cholangiocarcinoma

Objective To explore the clinical significance of promoter hypermethylation of O6-methylguanine-DNA methyltransferase(MGMT) in cholangiocarcinoma.Methods Promoter methylation status of MGMT gene and expression of MGMT protein were detected in cholangiocarcinoma by methylation-specific PCR and immunohistochemical staining,respectively.Results Aberrant methylation of MGMT gene was detected in 17 patients(47.2%).Twenty-one cases showed negative immunoreactivities.Of 21 patients with negative MGMT expression,14 patients had aberrant methylation of MGMT gene.In 15 patients with positive MGMT expression,aberrant methylation of MGMT gene was only found in three cases.There was a negative correlation between promoter methylation status of MGMT gene and the expression of MGMT protein(r_s=-0.816,P0.05).Promoter methylation status of MGMT gene was related to depth of invasion,degree of differentiation,and TNM stage(P0.05),but not to age of patient,gender,pathological type,and lymph node metastasis(P0.05).Conclusions Hypermethylation of MGMT promoter is a frequency molecular event in cholangiocarcinoma and may be involved in carcinogenesis.Methylation status of MGMT gene may be used to evaluate malignant degree of cholangiocarcinoma.