Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma
Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma
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DOI：
10.1016/j.ygyno.2010.09.003
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发表时间：
2011-01-01
影响因子：
4.7
通讯作者：
Butzow, Ralf
中科院分区：
文献类型：
--
作者：
Lassus, Heini;Staff, Synnove;Butzow, Ralf
Objective. Aurora-A是卵巢癌潜在的癌基因和治疗靶点。它参与有丝分裂事件，过表达导致中心体扩增和染色体不稳定。本研究旨在探讨Aurora-A和DNA倍体在浆液性卵巢癌中的临床意义。采用免疫组化法检测592例浆液性卵巢癌组织中Aurora-A蛋白表达，CISH法检测169例浆液性卵巢癌组织中Aurora-A拷贝数，实时荧光定量PCR法检测158例浆液性卵巢癌组织中Aurora-A mRNA表达，流式细胞仪检测440例浆液性卵巢癌组织中Aurora-A基因DNA倍体。Aurora-A在27%的肿瘤中过度表达，11%的肿瘤细胞质过度表达，17%的肿瘤细胞核过度表达。细胞质和细胞核的过度表达几乎是相互排斥的。细胞质和细胞核过度表达与较短的生存期、高级别、高增殖指数和异常p53相关。有趣的是，只有细胞质表达与非整倍性和磷酸化Aurora-A的表达相关。DNA倍体与患者预后差以及侵袭性临床病理参数相关。在多因素分析中，Aurora-A过表达是无病生存的独立预后因素，与分级、分期和倍体相关。Aurora-A蛋白表达与患者预后差和侵袭性疾病特征密切相关，这使得Aurora-A成为卵巢癌有前途的生物标志物和潜在的治疗靶点。细胞质和核Aurora-A蛋白可能具有不同的功能。DNA非整倍体是浆液性卵巢癌预后不良的强预测因子。(C)2010年爱思唯尔公司All rights reserved.
Objective. Aurora-A is a potential oncogene and therapeutic target in ovarian carcinoma. It is involved in mitotic events and overexpression leads to centrosome amplification and chromosomal instability. The objective of this study was to evaluate the clinical significance of Aurora-A and DNA ploidy in serous ovarian carcinoma.Methods. Serous ovarian carcinomas were analysed for Aurora-A protein by immunohistochemistry (n = 592), Aurora-A copy number by CISH (n = 169), Aurora-A mRNA by real-time PCR (n = 158) and DNA ploidy by flowcytometry (n = 440).Results. Overexpression of Aurora-A was found in 27% of the tumors, cytoplasmic overexpression in 11% and nuclear in 17%. The cytoplasmic and nuclear overexpression were nearly mutually exclusive. Both cytoplasmic and nuclear overexpression were associated with shorter survival, high grade, high proliferation index and aberrant p53. Interestingly, only cytoplasmic expression was associated with aneuploidy and expression of phosphorylated Aurora-A. DNA ploidy was associated with poor patient outcome as well as aggressive clinicopathological parameters. In multivariate analysis, Aurora-A overexpression appeared as an independent prognostic factor for disease-free survival, together with grade, stage and ploidy.Conclusions. Aurora-A protein expression is strongly linked with poor patient outcome and aggressive disease characteristics, which makes Aurora-A a promising biomarker and a potential therapeutic target in ovarian carcinoma. Cytoplasmic and nuclear Aurora-A protein may have different functions. DNA aneuploidy is a strong predictor of poor prognosis in serous ovarian carcinoma. (C) 2010 Elsevier Inc. All rights reserved.