胰腺导管腺癌中HER2/neu和拓扑异构酶Ⅱα基因的变化及相关性分析  

Topoisomerase Ⅱαand HER2/neu gene alterations and their correlation in pancreatic ductal adenocarcinomas

作　　者：梁智勇[1] 王文泽[1] 高洁[1] 武莎斐[1] 曾瑄[1] 刘彤华[1] 

机构地区：[1]中国医学科学院 中国协和医科大学 北京协和医院病理科,00730

出　　处：《中华病理学杂志》2007年第2期102-106,共5页Chinese Journal of Pathology

摘　　要：目的探讨胰腺导管腺癌(简称胰腺癌)中 HER2/neu 和拓扑异构酶Ⅱα(TOP2A)基因的变化及其意义。方法应用免疫组织化学(EnVision 法)和多色荧光原位杂交技术,检测26例中国人胰腺导管腺癌及癌旁胰腺组织、10例慢性胰腺炎组织、10例正常胰腺组织中 TOP2A 和 HER2/neu蛋白表达及基因状态的变化,分析蛋白表达与基因扩增间的关系,以及 TOP2A 和 HER2/neu 基因改变的相关性,并探讨二者与胰腺癌临床病理改变之间的关系。结果 26例胰腺癌组织中免疫组织化学显示 TOP2A 阳性表达指数从0.5%至70%,12例(46.2%)胰腺癌组织 HER2/neu 蛋白阳性表达。荧光原位杂交结果显示 TOP2A 和 HER2/neu 基因扩增的胰腺癌各10例(38.5%),其中9例为TOP2A 和 HER2/neu 共同扩增,癌旁胰腺组织、慢性胰腺炎及正常胰腺组织均未检测到 TOP2A和HER2/neu 蛋白表达及基因扩增。TOP2A 和 HER2/neu 蛋白表达水平与基因扩增无显著相关性(P>0.05)。TOP2A 和 HER2/neu 基因扩增具有显著的相关性(P<0.01)。结论胰腺癌中 TOP2A 和HER2/neu 的蛋白表达与基因扩增无相关性;TOP2A 和 HER2/neu 基因的共同扩增可能在胰腺癌发生发展中起重要作用,联合检测 TOP2A 和 HER2/neu 基因状态对于胰腺癌的靶向治疗可能具有一定的指导意义。Objective To investigate the changes of topoisomerase Ⅱα （TOP2A） and HER2/neu genes in pancreatic ductal adenocarcinomas of Chinese patients, and to determine their roles during carcinogenesis and tumor progression. Methods Expressions of TOP2A and HER2/neu proteins were detected by using immunohistochemistry, while gene amplifications of TOP2A and HER2/neu were assessed by using multi-color fluorescence in situ hybridization （FISH）. All the samples were of paraffin embedded and 10% formalin fixed tissue, including 26 cases of pancreatic ductal adenocarcinomas with adjacent nonneoplastic pancreatic tissues, 10 cases of chronic panreatitis, and 10 cases of normal pancreas. The correlation between TOP2A and HER2/neu gene status was analyzed. Results By immunohistochemistry, the nuclear positive index of TOP2A in pancreatic ductal adenocarcinomas varied from 0. 5% to 70%, and the positive rate of HER2/neu in pancreatic ductal adenocarcinomas was 46. 2% （12/26）. By FISH, 9/10 TOP2A amplified adenocarcinomas showed TOP2A and HER2/neu gene coamplification, while one case with HER2/neu gene amplification adenocarcinoma showed no TOP2A amplification. No expression of TOP2A, HER2/neu proteins and no amplification of TOP2A and HER2/neu gene were detected in adjacent nonneoplastic pancreatic tissues, chronic pancreatitis tissues and normal pancreas. No relationship was found between protein expression and gene amplification of TOP2A and HER2/neu （ P 〉 0.05 ）. TOP2A gene amplification was significantly correlated with HER2/neu gene amplification （ P 〈 0. 01 ）. Conclusions Protein expression of TOP2A and HER2/neu are not associated with the gene amplification. There is a significant correlation between TOP2A amplification and HER2/neu gene amplification. Co-amplification of TOP2A and HER2/neu may play an important role in the carcinogenesis and progression of pancreatic carcinoma. Evaluation of the status of TOP2A and HER2/neu may be helpful to achieve target therapy of pancreatic carcinoma.

关 键 词：胰腺肿瘤 DNA拓扑异构酶类 Ⅱ型 受体 ERBB-2 原位杂交 荧光 

分 类 号：R735.9[医药卫生—肿瘤]