Nuclear karyopherin α2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity
Nuclear karyopherin α2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity
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DOI：
10.1002/ijc.23628
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发表时间：
2008-09-15
影响因子：
6.4
通讯作者：
Hartmann, Arndt
中科院分区：
文献类型：
--
作者：
Gluz, Oleg;Wild, Peter;Hartmann, Arndt
乳腺癌患者淋巴结密集受累预示预后不良。其他分子预后因素在该亚组中的意义尚不清楚。核细胞蛋白- 2 （KPNA2）是乳腺癌发生发展的重要因素。本研究的目的是在随机WSG-AM-01试验中评估KPNA2表达对高危乳腺癌（HRBC）患者预后和强化化疗反应的影响。Kaplan-Meier和多变量Cox风险模型分析显示，KPNA2核表达（bbb10 % vs. 9个阳性淋巴结）与临床结局（中位随访63.3个月）相关，包括k-聚类确定的分子亚型（k = 5）。单因素分析显示，KPNA2过表达（n = 74,39%）与两个治疗组较短的无事件生存期和总生存期（OS）显著相关。多因素分析显示，KPNA2过表达是OS HR降低的独立预后因素= 1.86 [95% CI: 1.07-3.23, p = 0.03]。这一预测值与基底样/Her-2/neu亚型无关，与KPNA2显著相关，并特别针对G2肿瘤。我们的数据表明，在淋巴结阳性患者中，KPNA2核表达可作为新的预后指标，特别是在2个不同预后亚组G2肿瘤的判断中。KPNA2的表达也可能被认为是整体化疗耐药的标志，这是晚期乳腺癌常规化疗剂量调整无法克服的。(C) 2008 Wiley-Liss, Inc。
Intensive lymph node involvement indicates poor prognosis in breast cancer patients. The significance of other molecular prognostic factors in this subgroup is unclear. Karyopherin alpha 2 (KPNA2) has been reported as an important factor of tumorgenesis and progression of breast cancer. The aim of present study was to evaluate the impact of KPNA2 expression on prognosis of patients with high risk breast cancer (HRBC) and response intensive chemotherapy within the randomized WSG-AM-01 trial. KPNA2 nuclear expression (>10% vs. 9 positive lymph nodes and correlated with clinical outcome (median follow-up of 63.3 months) by Kaplan-Meier and multivariate Cox hazard model analysis, including, molecular subtypes determined by k-clustering (k = 5). KPNA2 overexpression (n = 74, 39%) significantly correlated with shorter event-free and overall survival (OS) in both therapy arms by univariate analysis. Multivariate analysis showed that the overexpression of KPNA2 was an independent prognostic factor of decreased OS HR = 1.86 [95% CI: 1.07-3.23, p = 0.03]. This predictive value was independent of basal-like/Her-2/neu subtypes, significantly associated with KPNA2 and was addressed particularly to G2 tumors. Our data suggest the use of KPNA2 nuclear expression as novel prognostic marker in node-positive patients, especially in determination of G2 tumors in 2 subgroups of different prognosis. KPNA2 expression may be also considered as a marker for global chemoresistance, which can not be overcome by conventional dose-modification of chemotherapy in advanced breast cancer. (C) 2008 Wiley-Liss, Inc.