中国人群胰腺癌与胃癌HER2/neu基因表达

Detection of HER2/neu Gene in Pancreatic and Gastric Adenocarcinoma among Chinese Patients

目的探讨胰腺癌与胃癌组织中HER2/neu基因表达状态及其在治疗与评估临床结局中的作用。方法应用免疫组织化学和多色荧光原位杂交技术,检测北京协和医院手术切除的81例胰腺导管癌及癌旁胰腺组织和100例胃癌及癌旁胃组织标本中HER2/neu蛋白表达及基因状态的变化,分析HER2/neu蛋白表达与基因状态间的关系及其与胰腺癌和胃癌临床病理改变间的关系。结果免疫组织化学显示,81例胰腺癌组织中9例(11.1%)HER2/neu蛋白表达阳性(2+及3+),100例胃癌组织中13例(13%)HER2/neu蛋白表达阳性(2+及3+);荧光原位杂交结果显示,81例胰腺癌组织中15例(18.5%)HER2/neu基因扩增,100例胃癌组织中11例(11%)HER2/neu基因扩增。胰腺癌HER2/neu基因扩增与淋巴结转移有显著相关性(P=0.001)。胃癌组织中6例HER2/neu蛋白3+病例均显示HER2/neu基因扩增,且胃癌组织HER2/neu蛋白表达与其基因扩增有显著相关性(P<0.0001)。无论是癌旁胰腺组织还是癌旁胃组织均未检测到HER2/neu蛋白表达及基因扩增。结论胰腺癌组织HER2/neu蛋白表达与基因扩增不一致,而胃癌组织HER2/neu蛋白表达与基因扩增有显著相关性。HER2/neu基因异常可能在胰腺癌及胃癌的发生发展中起着重要作用,对胰腺癌及胃癌患者进行HER2/neu基因状态检测可能对其靶向治疗具有一定的指导意义。

Objective To investigate the changes of HER2/neu gene in pancreatic and gastric adeno- carcinoma in Chinese patients and to evaluate its roles in targeted gene therapy. Methods The expression of HER2/neu protein was detected using immunohistochemistry, while gene amplifications of HER2/neu were assessed using multi-color fluorescence in situ hybridization （FISH）. The samples were paraffin embedded and 10% formalin fixed. They included 81 cases of pancreatic ductal adenocarcinomas with adjacent non-neoplastic pancreatic tissues and 100 cases of gastric adenocarcinomas with adjacent non-neoplastic gastric tisssues. Re- sults Immunohistochemical tests showed that the positive rate of HER2/neu in pancreatic ductal adenocarcinomas and gastric adenocarcinomas was 11.1% （9/81） and 13% （13/t00）, respectively. FISH showed that HER2/neu gene amplification was detected in 18.5% （15/81） of pancreatic adenocarcinoma cases 11% （11/100） of gastric adenocarcinoma （ including all 6 HER2/neu 3 ＋ cases）. HER2/neu protein expression and gene amplification were not found in adjacent normal tissues in both arms. Among the pancreatic adenocarcinoma cases, HER2/neu gene amplification was positively correlated with lymphoma metastasis （P = 0. 001 ）. Conclusions Protein expression is not relevant with gene amplification of HER2/neu in pancreatic cancer. HER2/neu gene amplification may be the major reason for its protein overexpression in gastric adenocarcinoma. HER2/neu gene expression may play an important role in the carcinogenesis of pancreatic and gastric adenocarcinoma. Evaluation of the status of HER2/neu may be helpful to achieve the targeted therapy of pancreatic and gastric adenocarcinoma.