[Aurora-a是III期上皮性卵巢癌的预测指标]。

S Lassmann, Y Shen, U Jütting, P Whiele, A Walch, G Gitsch, A Hasenburg, M Werner
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摘要

目的:Aurora-A/STK15激酶(以下简称AUKRA)在多种上皮性癌症中均有过表达,如胃肠道和妇科癌。然而,它作为晚期卵巢癌患者辅助治疗的预后和/或预测标志物的作用尚不清楚。因此,本研究旨在确定(1)115例卵巢癌患者AURKA表达(mRNA和蛋白)的临床价值;(2)AURKA在DNA水平上过表达的基础。方法:福尔马林固定和石蜡包埋组织标本(卵巢癌:n=115;非肿瘤卵巢:n=28),按照标准化方案进行显微解剖和定量RT-PCR以及组织微阵列半定量免疫组化(IHC)。在一组病例(n=37)中进行荧光原位杂交(FISH)分析AURKA DNA拷贝数。结果:与非肿瘤卵巢相比,卵巢癌中AURKA mRNA和蛋白水平的表达显著升高(p < 0.0001)。107例患者中有68例(63.5%)出现AURKA蛋白过表达。对于III期卵巢癌患者进行了最佳减瘤治疗并接受了辅助紫杉烷化疗,AURKA过表达与延长总生存期显著相关(p = 0.02)。最后,AURKA过表达与AURKA DNA拷贝数增加相关(p = 0.01)。结论:总之,AURKA过表达在DNA水平上受到调控,是一种新的预测III期卵巢癌亚组患者的标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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[Aurora-a is a predictive marker for stage III epithelial ovarian cancers].

Aim: Overexpression of Aurora-A/STK15 kinase (hereafter AUKRA) is seen in a variety of epithelial cancers, such as gastrointestinal and gynaecological carcinomas. Its role as prognostic and/or predictive marker for adjuvant therapy of patients with advanced ovarian cancer is however still unclear. Therefore, the present study aimed at determining (1) the clinical value of AURKA expression (mRNA and protein) in 115 patients with ovarian carcinomas and (2) the basis of AURKA overexpression at the DNA level.

Methods: Formalin-fixed and Paraffin-embedded tissue samples (ovarian carcinoma: n=115; non-neoplastic ovaries: n=28) were processed for microdissection and quantitative RT-PCR as well as for semi-quantitative immunohistochemistry (IHC) of tissue microarrays according to standardised protocols. Fluorescence in Situ Hybridisation (FISH) was performed in a sub-set of cases (n=37) to analyse AURKA DNA copy numbers.

Results: The results demonstrate significantly elevated AURKA expression at the mRNA and protein level in ovarian carcinomas as compared to non-neoplastic ovaries (p < 0.0001). AURKA protein overexpression was observed in 68/107 (63.5%) of cases. For patients with stage III ovarian carcinoma having been optimally debulked and receiving adjuvant Taxane-based chemotherapy, AURKA overexpression was significantly linked to prolonged overall survival (p = 0.02). Finally AURKA overexpression was associated with increased AURKA DNA copy numbers (p = 0.01).

Conclusion: In summary, AURKA overexpression, which is regulated at the DNA level, is a novel predictive marker for a subgroup of patients with stage III ovarian carcinomas.

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