Liang Zhi-Yong, Wang Wen-Ze, Gao Jie, Wu Sha-Fei, Zeng Xuan, Liu Tong-Hua
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
Zhonghua Bing Li Xue Za Zhi. 2007 Feb;36(2):102-6.
To investigate the changes of topoisomerase IIalpha (TOP2A) and HER2/neu genes in pancreatic ductal adenocarcinomas of Chinese patients, and to determine their roles during carcinogenesis and tumor progression.
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 non-neoplastic pancreatic tissues, 10 cases of chronic panreatitis, and 10 cases of normal pancreas. The correlation between TOP2A and HER2/neu gene status was analyzed.
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 non-neoplastic 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).
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.
研究中国患者胰腺导管腺癌中拓扑异构酶IIα（TOP2A）和HER2/neu基因的变化，并确定它们在致癌过程和肿瘤进展中的作用。
采用免疫组织化学法检测TOP2A和HER2/neu蛋白的表达，同时采用多色荧光原位杂交（FISH）法评估TOP2A和HER2/neu基因的扩增情况。所有样本均为石蜡包埋、10%中性福尔马林固定的组织，包括26例胰腺导管腺癌及相邻的非肿瘤性胰腺组织、10例慢性胰腺炎组织和10例正常胰腺组织。分析TOP2A和HER2/neu基因状态之间的相关性。
免疫组织化学检测显示，胰腺导管腺癌中TOP2A的细胞核阳性指数为0.5%至70%，HER2/neu的阳性率为46.2%（12/26）。FISH检测显示，10例TOP2A扩增的腺癌中有9例表现为TOP2A和HER2/neu基因共扩增，而1例HER2/neu基因扩增的腺癌未表现出TOP2A扩增。在相邻的非肿瘤性胰腺组织、慢性胰腺炎组织和正常胰腺组织中未检测到TOP2A、HER2/neu蛋白表达及TOP2A和HER2/neu基因扩增。TOP2A和HER2/neu的蛋白表达与基因扩增之间无相关性（P>0.05）。TOP2A基因扩增与HER2/neu基因扩增显著相关（P<0.01）。
TOP2A和HER2/neu的蛋白表达与基因扩增无关。TOP2A扩增与HER2/neu基因扩增之间存在显著相关性。TOP2A和HER2/neu的共扩增可能在胰腺癌的发生和进展中起重要作用。评估TOP2A和HER2/neu的状态可能有助于实现胰腺癌的靶向治疗。
