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O(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)在胃肠胰神经内分泌肿瘤中的表达及其临床意义

Expression of O(6)-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm.

作者信息

Yang Qiu-Chen, Wang Yu-Hong, Lin Yuan, Xue Ling, Chen Yuan-Jia, Chen Min-Hu, Chen Jie

机构信息

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, China.

Department of Clinical Pathology, The First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, China.

出版信息

Int J Clin Exp Pathol. 2014 Jun 15;7(7):4204-12. eCollection 2014.

Abstract

O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O(6)-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (χ(2) = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP-NEN.

摘要

O(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)是一种广泛存在的DNA修复酶,可抵御鸟嘌呤O(6)-烷基化剂引起的突变。到目前为止,我们对MGMT在胃肠胰神经内分泌肿瘤(GEP-NEN)中的表达了解甚少。为了研究MGMT在GEP-NEN中的表达及其临床意义,我们检测了174例GEP-NEN标本,其中152例标本来自中山大学附属第一医院1995年10月至2013年11月期间,22例标本来自北京协和医院2004年9月至2010年4月期间。采用EnVision免疫组化染色法检测MGMT蛋白。同时收集并分析临床病理因素。我们观察到MGMT的总体表达率为83.9%。MGMT蛋白的过表达与性别、年龄、功能状态、原发肿瘤部位、分级、分类、TNM分期及转移均无关(P>0.05)。Kaplan-Meier分析显示,GEP-NEN患者中MGMT阳性和MGMT阴性肿瘤的生存率无显著差异(χ(2)=0.887,P=0.346)。在Cox比例风险回归模型进行的多因素分析中,MGMT表达也不是生存的独立预测因素。这些结果表明,MGMT蛋白在GEP-NEN中高表达。胰腺NEN和胃肠道NEN中的MGMT缺陷率相似。MGMT表达与GEP-NEN的预后无关。

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