Engelstaedter Verena, Schiffers Jennifer, Kahlert Steffen, Mainka Patrick, Engel Jutta, Kirchner Thomas, Diebold Joachim, Mayr Doris
Department of Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians-University Munich, Munich, Germany.
Diagn Mol Pathol. 2012 Jun;21(2):77-83. doi: 10.1097/PDM.0b013e31823b6e43.
Her-2/neu gene amplification is an established prognostic factor in breast cancer, and Her-2/neu protein is the target of the therapeutic monoclonal antibody Herceptin. More recently, topoisomerase IIα became a new focus of breast cancer research because of its role as a target for anthracycline therapy. Therefore, we compared Her-2/neu and topoisomerase IIα amplification/deletion in a large series of advanced breast cancer using fluorescence in situ hybridization. Paraffin-embedded archival tissue from 245 patients was retrieved and assessed for Her-2/neu and topoisomerase IIα amplification/deletion by fluorescence in situ hybridization according to standard protocols. Relation to clinical data and survival was sought. A total of 245 cases were analyzed. Amplification for Her-2/neu was seen in 57 cases (23.3%), and for topoisomerase IIα in 12 cases (4.9%). Coamplification was found in 9 samples (3.7%), 3 cases (1.2%) showed amplification of topoisomerase IIα but not of Her-2/neu, and 48 samples (19.8%) displayed amplification for Her-2/neu but not for topoisomerase IIα. Correlation to the histologic type, the stage, or the grade could not be found. Only the amplification of topoisomerase IIα was associated with very poor outcome; survival of cases with amplification of Her-2/neu only was slightly lower than the mean overall survival (27.4 vs. 31.9 mo). Amplification of Her-2/neu and/or topoisomerase IIα is associated with poor overall survival. Amplification of topoisomerase IIα does not seem to be necessarily linked to Her-2/neu-amplification. However, independent determination of these 2 markers seems to be valuable for an individualized therapy of breast cancer patients.
Her-2/neu基因扩增是乳腺癌中已确定的预后因素，Her-2/neu蛋白是治疗性单克隆抗体赫赛汀的靶点。最近，拓扑异构酶IIα因其作为蒽环类药物治疗靶点的作用而成为乳腺癌研究的新焦点。因此，我们使用荧光原位杂交技术比较了一大系列晚期乳腺癌中Her-2/neu和拓扑异构酶IIα的扩增/缺失情况。检索了245例患者的石蜡包埋存档组织，并根据标准方案通过荧光原位杂交评估Her-2/neu和拓扑异构酶IIα的扩增/缺失情况。探寻其与临床数据和生存情况的关系。共分析了245例病例。57例（23.3%）出现Her-2/neu扩增，12例（4.9%）出现拓扑异构酶IIα扩增。9个样本（3.7%）发现共扩增，3例（1.2%）显示拓扑异构酶IIα扩增但Her-2/neu未扩增，48个样本（19.8%）显示Her-2/neu扩增但拓扑异构酶IIα未扩增。未发现与组织学类型、分期或分级相关。只有拓扑异构酶IIα的扩增与极差的预后相关；仅Her-2/neu扩增病例的生存期略低于总体平均生存期（27.4个月对31.9个月）。Her-2/neu和/或拓扑异构酶IIα的扩增与总体生存期差相关。拓扑异构酶IIα的扩增似乎不一定与Her-2/neu扩增相关。然而，独立检测这两个标志物似乎对乳腺癌患者的个体化治疗有价值。
