上皮性卵巢癌中拓扑异构酶II-α和HER-2基因的扩增及表达率

Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma.

作者信息

Mano M S, Awada A, Di Leo A, Durbecq V, Paesmans M, Cardoso F, Larsimont D, Piccart M

机构信息

Unité de Chimiothérapie, Institut Jules Bordet, Brussels, Belgium.

出版信息

Gynecol Oncol. 2004 Mar;92(3):887-95. doi: 10.1016/j.ygyno.2003.12.010.

DOI:10.1016/j.ygyno.2003.12.010

PMID:14984957

Abstract

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 > or =1.5 and > or =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 IHC, 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.

摘要

目的

拓扑异构酶II-α（T2a）作为乳腺癌（BC）中蒽环类药物反应的潜在预测标志物正在进行积极研究。尽管T2a抑制剂作为上皮性卵巢癌（EOC）一线和挽救治疗的作用仍不明确，但我们推测一小部分卵巢癌患者可能从这些药物中获得选择性益处。在本研究中，我们分别通过荧光原位杂交（FISH）和免疫组织化学（IHC）研究了T2a和HER-2扩增及过表达的实际发生率。

方法

从我们的存档中选取73例未经化疗的EOC患者样本。大多数患者可获得国际妇产科联盟（FIGO）分期和组织学信息。

结果

基于≥1.5和≥2（拷贝数/着丝粒17比值）的任意临界值，HER-2的扩增率分别为15/64（23.4%）和8/64（12.5%），而T2a的扩增率分别为16/64（25%）和5/64（7.8%）。我们仅发现3/72（4.2%）例HER-2过表达（3+），而T2a过表达（>10%的细胞染色）为15/70（21.4%）。当将这些标志物作为连续变量分析时，T2a扩增与过表达之间存在适度相关性（P=0.01），T2a与HER-2扩增之间存在强相关性（P<0.001）。T2a扩增与FIGO晚期显著相关（P=0.02）。