胆囊腺癌及癌旁组织中MGMT、hMLH1、hMSH2基因的表达和临床意义

摘要

目的 研究胆囊腺癌、癌旁组织和腺瘤性息肉中MGMT、hMLH1和hMSH2基因的表达水平及意义.方法 共收集80例腺癌、25例癌旁组织和25例腺瘤性息肉手术切除标本,常规石蜡包埋切片,EnVision免疫组化法检测MGMT、hMLH1和hMSH2表达水平.结果 胆囊腺癌组织中MGMT、hMLH1和hMSH2阳性表达率明显低于癌旁组织和腺瘤性息肉(P＜0.01).癌旁组织与腺瘤性息肉MGMT、hMLH1和hMSH2的阳性表达率差异无统计学意义(P＞0.05).高分化、肿块最大径≤3 cm、无淋巴结转移和未侵犯周围组织患者组织标本中MGMT、hMLH1和hMSH2的表达阳性率明显高于低分化、肿块最大径＞3 cm、淋巴结转移和侵犯周围组织的患者(P＜0.05).Kaplan-Meier生存分析显示MGMT、hMLH1和hMSH2表达阳性胆囊腺癌患者的平均生存期明显高于阴性患者(P＜0.05).Cox多因素分析显示MGMT、hMLH1和hMSH2阳性表达与术后生存率呈正相关,与病死率呈负相关;组织中MGMT、hMLH1和hMSH2的阳性表达是胆囊腺癌术后的独立预后因子和保护性因素.结论 MGMT、hMLH1和hMSH2表达反映了胆囊腺癌的发生、进展和预后.MGMT、hMLH1和hMSH2阳性表达的腺癌患者预后较好.%Objective To investigate the gene expressions of MGMT,hMLH1 and hMSH2 in gallbladder adenocarcinoma,tumor adjacent tissues and adenomatous polyp,and to explore the clinicopathological significance.Methods The EnVision immunohistochemical method was used to detect the expressions of MGMT,hMLH1 and hMSH2 in routine paraffin-embedded sections of tissue samples of gallbladder adenocarcinoma (n =80),tumor adjacent tissues (n =25) and adenomatous polyp (n =25).Results The positive rates of MGMT,hMLH1 and hMSH2 were significantly lower in gallbladder adenocarcinoma than those in tumor adjacent tissues and adenomatous polyp (P ＜ 0.05).The positive rates were significantly higherin specimens with well-differentiated adenocarcinoma,no lymph node metastasis and no infiltrated regional tissues or organs than in specimens with low-differentiated adenocarcinoma,lymph node metastasis and infiltrated regional tissues or organs (P ＜ 0.05).Univariate Kaplan-Meier analysis showed that low expressions of MGMT,hMLH1 and hMSH2 were significantly associated with better overall survival (P ＜0.05).Cox regression analysis showed that positive expressions of MGMT,hMLH1 and hMSH2 were positively correlated with survival.Conclusions The expressions of MGMT,hMLH1 and hMSH2 might be important biological markers for predicting carcinogenesis,progression,biological behaviors and prognosis in gallbladder adenocarcinoma.The specimens showing positive expressions of MGMT,hMLH1 and hMSH2 were associated with good prognosis.