Expression of DNA methyltransferases in hilar cholangiocarcinoma and its clinical significance / 中华消化外科杂志

ABSTRACT

Objective To investigate the expression of DNA methyltransferases ( DNMTs) in hilar cholangiocarcinoma and its clinical significance.Methods A total of 150 samples of cholangetic tissues were collected from 111 patients with hilar cholangiocarcinoma ( cholangiocarcinoma group) and 39 patients with choledochocele ( control group) at the First Affiliated Hospital of Sun Yat-Sen University from April 1997 to March 2007.A tissue chip containing the samples of hilar cholangiocarcinoma and choledochocele was prepared.Expressions of DNMT1,DNMT3a and DNMT3b were detected by the immunohistochemical staining. Differences in the protein expressions of DNMTs in the cholangiocarcinoma group and the control group were compared,and the correlation between DNMTs protein expressions and clinicopathological features was analyzed.All data were analyzed by using the chi-square test or Fisher exact probability.The survival curve was drawn by using the Kaplan-Meier method and the survival rate was compared by using the Log-rank test.Results The rates of high protein expressions of DNMT1 and DNMT3b were 54.1％ (60/111) and 47.7％ (53/111) in the cholangiocarcinoma group, which were significantly higher than 28.2％ ( 11/39) and 23.1％ ( 9/39) in the control group　( x2 =7.740,7.240,P ＜0.05). The high protein expression of DNMT1 was correlated with-the Bismuth-Corlette classification and T staging of the tumor ( x2 =12.200, 17.800,P ＜0.05) ; there was no significant difference in the high protein expressions of DNMT3a in the cholangiocarcinoma group and the control group ( x2 =3.370.P ＞0.05 ) ; while the high protein expressions of DNMT3b was correlated with the Bismuth-Corlette classification (x2 =8.300,P ＜ 0.05 ),but not with the T staging. Sixty-six patients received hilar cholangiocarcinoma resection,and 42 of them were followed up.The median postoperative survival time of patients with low protein expression of DNMT1 was 23.9 months,which was significantly longer than 11.8 months of patients with high protein expression of DNMT1 (x2 =3.980,P ＜ 0.05).Conclusions DNMT1 and DNMT3b with high protein expression might play important roles in the carcinogenesis and development of hilar cholangiocarcinoma.There is an obvious relationship between the expression of DNMT1 and postoperative survival time of patients with hilar cholangiocarcinoma,and DNMT1 might be a valuable prognostic factor for hilar cholangiocarcinoma.