Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer
Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer
复制标题
DOI：
10.1007/s10549-006-9492-5
复制
发表时间：
2007-12-01
影响因子：
3.8
通讯作者：
Reis-Filho, Jorge S.
中科院分区：
文献类型：
--
作者：
Arriola, Edurne;Rodriguez-Pinilla, Socorro Maria;Reis-Filho, Jorge S.
研究背景TOP 2A基因编码拓扑异构酶II α，是蒽环类药物的直接分子靶点。该基因经常与HER 2共扩增。本研究的目的是分析模式的TOP 2A扩增和蛋白质表达的乳腺癌的分子亚组，并定义的影响TOP 2A扩增的一系列患者均匀治疗的结果与辅助anthracyclines.Methods一个队列的245例早期乳腺癌患者均匀治疗的辅助设置蒽环类药物。使用含有这些癌症的组织微阵列通过显色原位杂交测定HER 2和TOP 2A基因拷贝数。还使用单克隆抗体（Ki-S1）进行拓扑异构酶II α的免疫组织化学染色。TOP 2A扩增和蛋白表达与经典的预后参数、免疫组化标记物的表达以及使用替代免疫组化标记物的基因表达谱分类相关。结果TOP 2A扩增仅限于HER 2扩增的肿瘤，且与ER阳性相关。在HER 2扩增肿瘤患者亚组中，TOP 2A扩增预测了更好的总生存期和无病生存期（分别为P = 0.028和0.026）。结论TOP 2A基因扩增可能是预测蒽环类药物疗效的有用指标。
Background TOP2A gene encodes topoisomerase II alpha, the direct molecular target of anthracyclines. This gene is frequently coamplified with HER2. The aims of this study were to analyse the pattern of TOP2A amplification and protein expression in relation to the molecular subgroups of breast cancers; and to define the impact of TOP2A amplification on the outcome of a series of patients homogeneously treated with adjuvant anthracyclines.Methods A cohort of 245 patients with early breast cancer homogeneously treated with anthracyclines in the adjuvant setting was selected. A tissue microarray containing these cancers was used to determine HER2 and TOP2A gene copy number by means of chromogenic in situ hybridization. Immunohistochemical staining of topoisomerase II alpha was also performed using a monoclonal antibody (Ki-S1). TOP2A amplification and protein expression were correlated with classical prognostic parameters, expression of immunohistochemical markers and with a gene expression profiling classification using surrogate immunohistochemical markers. Kaplan-Meier method was used to construct survival curves and results were compared with log-rank test.Results TOP2A amplification was restricted to tumours with HER2 amplification and was significantly associated with ER positivity. In the subgroup of patients with HER2 amplified tumours, TOP2A amplification predicted a better overall survival and disease free survival (P = 0.028 and 0.026, respectively). On multivariate analysis, TOP2A amplification maintained its predictive value for DFS.Conclusion TOP2A amplification is likely to be a useful marker to predict the subset of patients who will benefit from anthracyclines.