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Aurora-B 蛋白的表达与 III 期卵巢癌一线基于紫杉烷类化疗的初始反应相关。

Aurora-B protein expression is linked to initial response to taxane-based first-line chemotherapy in stage III ovarian carcinoma.

机构信息

Department of Obstetrics and Gynaecology, University Medical Center, Freiburg, Germany.

出版信息

J Clin Pathol. 2012 Jan;65(1):29-35. doi: 10.1136/jclinpath-2011-200212. Epub 2011 Oct 19.

Abstract

AIMS

Aurora kinases are central to cell proliferation and considered to be prognostic/predictive markers and therapeutic targets for epithelial cancers. Here, the prognostic/predictive value of Aurora-B protein expression was evaluated in patients with serous, FIGO stage III ovarian carcinomas treated with taxane- or platinum-based first-line chemotherapy (1st-CTx).

METHODS

Immunohistochemistry was performed on tissue microarrays, including 80 ovarian carcinomas and 18 non-neoplastic ovaries, previously characterised for Aurora-A protein expression. None or marginal (score 0+1), moderate (score 2) and strong (score 3) Aurora-B protein expression was correlated with clinico-pathological parameters as well as recurrence-free survival (RFS) and overall survival (OS).

RESULTS

While non-neoplastic ovaries were negative for Aurora-B, almost all (79/80; 99%) ovarian carcinomas exhibited Aurora-B positive tumour cells, with score 1 in 41/80 (51%), score 2 in 23/80 (29%) and score 3 in 15/80 (19%) cases. Aurora-B and Aurora-A protein expression correlated significantly (p=0.002). In optimal debulked patients, Aurora-B protein expression was associated with RFS (p=0.011, n=53) and marginally with OS (p=0.460; n=53). Moreover, Aurora-B protein expression was predictive for RFS of optimal debulked patients with taxane-based (p=0.006; n=32), but not with platinum-based (p=0.720; n=20) 1st-CTx. Aurora-B protein expression was not linked to OS in optimal debulked patients with either of the two 1st-CTx.

CONCLUSIONS

Aurora-B protein expression frequently occurs in serous, FIGO stage III ovarian carcinomas, making it a 'drugable' molecular target in the majority of ovarian carcinoma patients. Moreover, Aurora-B protein expression is predictive for initial response to taxane-based 1st-CTx in optimal debulked, late stage ovarian carcinoma patients.

摘要

目的

极光激酶在细胞增殖中起核心作用,被认为是上皮性癌症的预后/预测标志物和治疗靶点。在此,评估了 Aurora-B 蛋白表达在接受紫杉烷类或铂类为基础的一线化疗(1 线 CTx)治疗的浆液性、FIGO 分期 III 卵巢癌患者中的预后/预测价值。

方法

使用组织微阵列进行免疫组织化学检测,包括 80 例卵巢癌和 18 例非肿瘤性卵巢,先前已对 Aurora-A 蛋白表达进行了特征分析。无或边缘(评分 0+1)、中度(评分 2)和强(评分 3)Aurora-B 蛋白表达与临床病理参数以及无复发生存(RFS)和总生存(OS)相关。

结果

非肿瘤性卵巢呈 Aurora-B 阴性,而几乎所有(79/80;99%)卵巢癌均有 Aurora-B 阳性肿瘤细胞,其中 41/80(51%)为评分 1,23/80(29%)为评分 2,15/80(19%)为评分 3。Aurora-B 和 Aurora-A 蛋白表达呈显著相关性(p=0.002)。在最佳减瘤患者中,Aurora-B 蛋白表达与 RFS 相关(p=0.011,n=53),与 OS 相关(p=0.460;n=53)则为边缘性相关。此外,Aurora-B 蛋白表达对紫杉烷类为基础的 1 线 CTx 最佳减瘤患者的 RFS 具有预测作用(p=0.006;n=32),而对铂类为基础的 1 线 CTx 无预测作用(p=0.720;n=20)。在两种 1 线 CTx 治疗的最佳减瘤患者中,Aurora-B 蛋白表达与 OS 无关。

结论

Aurora-B 蛋白表达在浆液性、FIGO 分期 III 卵巢癌中频繁发生,使其成为大多数卵巢癌患者的“可治疗”分子靶点。此外,Aurora-B 蛋白表达对最佳减瘤的晚期卵巢癌患者初始对紫杉烷类为基础的 1 线 CTx 的反应具有预测作用。

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