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目的通过对DNA甲基转移酶(DNMT)在涎腺腺样囊性癌(ACC)中表达的检测,分析DNMT与ACC抑癌基因甲基化、生物学行为的相关性,探讨DNMT在ACC发生、发展中的作用。方法对60例ACC临床病理标本进行DNMT1、DNMT3b的免疫组化染色,显微镜观察,将观察结果与p16、RASSF1A、DAPK、MGMT、E-cadherin多个抑癌基因的甲基化状况、病理分级、临床分期进行比较,应用Fisher确切概率法进行统计学分析。结果①DNMT1在ACC中的阳性表达程度明显高于DNMT3b的阳性表达(P<0．01)。②DNMT1阳性表达随发生甲基化的抑癌基因个数的增加而增加,DNMT1高、低表达组与抑癌基因高、低甲基化组之间差异有统计学意义(P<0．05),与RASSF1A基因的甲基化呈相关性(P<0．01)。③DNMT1的阳性表达程度与ACC病理分级(P<0．05)、临床分期(P< 0．01)呈正相关,实性成分越多、分期越晚,表达越高。④未发现DNMT3b与抑癌基因的甲基化状况、病理分级、临床分期间的相关性。结论DNMT1可能是ACC体内对维持抑癌基因甲基化起主导作用的甲基化酶,与RASSF1A基因的甲基化、ACC病理分级、临床分期有相关性,在ACC的发生、发展中扮演着重要角色,有可能作为肿瘤预后的评估指标之一。
Objective To detect the association between DNMT and ACC oncogene methylation and biological behavior by detecting the expression of DNA methyltransferase (DNMT) in salivary adenoid cystic carcinoma (ACC) and to investigate the role of DNMT in ACC , The role of development. Methods Immunohistochemical staining of DNMT1 and DNMT3b in 60 cases of clinical and pathological specimens of ACC was observed by microscope. The results were compared with the methylation status of multiple tumor suppressor genes p16, RASSF1A, DAPK, MGMT and E-cadherin, pathological grade, Clinical staging were compared using Fisher exact probability method for statistical analysis. Results ① The positive expression of DNMT1 in ACC was significantly higher than that in DNMT3b (P <0.01). ② The positive expression of DNMT1 increased with the increase of the number of methylated tumor suppressor genes. There was a significant difference between DNMT1 high and low expression group and high and low methylated tumor suppressor gene (P <0.05) , Which was correlated with the methylation of RASSF1A gene (P <0.01). ③ The positive expression of DNMT1 was positively correlated with the pathological grading of ACC (P <0.05) and clinical stage (P <0.01). The more positive components, the later the stage, the higher the expression of DNMT1. ④Not found DNMT3b and tumor suppressor gene methylation status, pathological grade, clinical stage of the correlation. Conclusions DNMT1 may be the methylation enzyme that plays a leading role in maintaining methylation of tumor suppressor gene in ACC, which is related to the methylation of RASSF1A gene, the pathological grading of ACC and clinical stage, and plays an important role in the occurrence and development of ACC Important role, it may be as one of the prognostic indicators of cancer.