Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes
Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes
复制标题
DOI：
10.1080/02841860310019007
复制
发表时间：
2004-01-01
期刊：
影响因子：
3.1
通讯作者：
Overgaard, J
中科院分区：
文献类型：
--
作者：
Olsen, KE;Knudsen, H;Overgaard, J
改善乳腺癌患者治疗的新策略侧重于HER2癌蛋白对传统治疗方案的反应以及针对该蛋白的新药的效果。此外，拓扑异构酶IIα(TOP2A)基因的状态被认为是蒽环类药物治疗的预测标志。在这项对120个肿瘤的研究中，用HercepTest(TM)免疫组织化学检测HER2过表达，并与用一种新的HER2探针进行荧光原位杂交(FISH)研究的HER2基因扩增进行了比较。此外，还评价了HercepTest作为筛选TOP2A基因异常的FISH筛查工具的价值。HercepTest评分3+在30个扩增的肿瘤中有27个发现了HER2基因扩增(敏感度为0.90)，假阴性率为0.10，假阳性率为0.06。TOP2A基因扩增或缺失20例。这些癌症中有16例(80%)属于HercepTest3+组，但有4例肿瘤的TOP2A基因发生了变化，HER2状态正常。传统上，在FISH技术中，结果是基于对60个细胞的计数。然而，我们发现，一种耗时少得多的计算60个信号的方法也得到了同样好的结果。
New strategies for improving treatment of patients with breast carcinoma have focused on the HER2 oncoprotein with regard to response to traditional therapy regimes and the effect of a new drug specifically directed against the protein. Furthermore, the status of the topoisomerase IIalpha (TOP2A) gene has been suggested as a predictive marker of anthracycline treatment. In this study of 120 tumours, immunohistochemically detected HER2 overexpression with HercepTest(TM) has been compared to the HER2 gene amplification investigated with a new HER2 probe for fluorescence in situ hybridization (FISH). In addition, the HercepTest was evaluated as a screening tool for choosing cases for FISH investigation of TOP2A gene aberrations. The HercepTest score 3+ identified HER2 gene amplification in 27 of 30 amplified tumours (sensitivity of 0.90) with a false-negative rate of 0.10 and a false-positive rate of 0.06. TOP2A gene amplification or deletion was found in 20 cases. Sixteen (80%) of these carcinomas were in the HercepTest 3+ group, but four tumours had alterations in the TOP2A gene with normal HER2 status. Traditionally, in the FISH technique the result has been based on counting 60 cells. However, we found that a much less time-consuming method of counting 60 signals gave equally good results.