Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients.
Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients.
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DOI：
10.1016/j.ejca.2017.06.019
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Heestand GM;Schwaederle M;Gatalica Z;Arguello D;Kurzrock R
拓扑异构酶I （TOPO1）和拓扑异构酶Iα (TOP2A)是多种化疗药物的特异性靶点。TOPO1蛋白表达的增加和TOP2A基因的扩增分别与结直肠癌和乳腺癌的治疗反应有关。TOPO1和TOP2A也可能是其他恶性肿瘤的潜在治疗靶点。我们分析了不同癌症患者（n = 24262例）的TOPO1蛋白表达和TOP2A基因扩增。由于研究了HER2和TOP2A共扩增对蒽环类药物疗效的预测价值，我们也分析了HER2扩增的标本。51%的肿瘤中存在TOPO1蛋白过表达。4%的肿瘤有TOP2A扩增，胆囊肿瘤和胃食管/食道肿瘤的比例超过10%。总共有4903份标本进行了TOP2A和HER2扩增检测；共扩增129例（2.6%）。在乳腺癌、卵巢癌、胃食管/食管癌和胰腺癌的TOP2A扩增患者中，HER2扩增率高（bbb40 %）。我们的数据表明，在多种恶性肿瘤中存在TOPO1表达和TOP2A扩增增加以及HER2共改变。这些观察结果对传统上不用于这些肿瘤类型的化疗的敏感性的影响值得研究。
Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well. We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well. Overexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer. Our data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation.
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