Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma
Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma
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DOI：
10.1016/j.ygyno.2003.12.010
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发表时间：
2004-03-01
影响因子：
4.7
通讯作者：
Piccart, M
中科院分区：
文献类型：
--
作者：
Mano, MS;Awada, A;Piccart, M
目标。拓扑异构酶II-α(T2a)正在被积极研究，作为乳腺癌(BC)对蒽环类药物反应的潜在预测标记物。尽管T2a抑制剂作为上皮性卵巢癌(EOC)前期和挽救治疗的作用尚不清楚，但我们推测，一小部分卵巢癌患者可以从这些药物中获得选择性好处。在本研究中，我们分别用荧光原位杂交(FISH)和免疫组织化学(IHC)方法检测T2a和HER-2的扩增和过表达。从我们的档案中选取73例化疗初治的卵巢癌患者的标本。大多数患者的FIGO分期和组织学检查是可行的。根据大于或等于1.5和大于或等于2(拷贝/着丝粒比率17)的任意截断值，HER-2的扩增率分别为15/(23.4%)和8/(12.5%)，而T2a的扩增率为16/(25%)和5/(7.8%)。我们发现仅3/72例(4.2%)HER-2过度表达(3+)，而15/70例(21.4%)T2a(染色10%的细胞)。当将T2a扩增与HER-2扩增作为连续变量进行分析时，T2a扩增与HER-2过度表达之间存在中度相关性(P=0.001)，而T2a扩增与HER-2扩增之间存在强相关性(P<；0.001)。T2a扩增与晚期FIGO分期显著相关(P=0.02)。FISH和IFIC分别检测HER-2和T2a的扩增和过表达在卵巢癌中是可行的。这些检测可用于大规模评估这些标记物在未来的潜在预测和预后价值。需要进一步的研究，特别是对T2a的研究，以确定未来潜在临床使用的最佳切割点。(C)2004 Elsevier Inc.保留所有权利。
Objectives. Topoisomerase II-alpha (T2a) is being actively investigated as a potential predictive marker of response to anthracyclines in breast cancer (BC). Although the role of T2a inhibitors as upfront and salvage treatment for epithelial ovarian carcinoma (EOC) remains unclear, we speculated that a small subgroup of ovarian cancer patients could derive a selective benefit from these agents. In this study, we investigated the actual rates of T2a and HER-2 amplification and overexpression by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively.Methods. Seventy-three samples of chemotherapy-naive patients with EOC were selected from our archives. FIGO stage and histology were available for most patients.Results. Based on arbitrary cut-offs of greater than or equal to 1.5 and greater than or equal to 2 (ratio copies/centromere17), amplification rates for HER-2 were 15/64 (23.4%) and 8/64 (12.5%) versus 16/64 (25%) and 5/64 (7.8%) for T2a. We found only 3/72 (4.2%) cases of HER-2 overexpression (3+) versus 15/70 (21.4%) for T2a (staining of > 10% of the cells). There was a modest correlation between T2a amplification and overexpression (P = 0.01) and a strong correlation between T2a and HER-2 amplification when these markers were analysed as continuous variables (P < 0.001). T2a amplification significantly correlated with advanced FIGO stage (P = 0.02).Conclusion. The assessment of HER-2 and T2a amplification and overexpression by FISH and IFIC, respectively, is feasible in EOC. These tests can be used for large-scale evaluation of the potential predictive and prognostic value of these markers in the future. Further studies with a special focus on T2a are needed to determine the best cut-offs for potential clinical use in the future. (C) 2004 Elsevier Inc. All rights reserved.