Span Paul N, Sweep Fred C G J, Wiegerinck Erwin T G, Tjan-Heijnen Vivianne C G, Manders Peggy, Beex Louk V A M, de Kok Jaques B
Departments of Chemical Endocrinology, Clinical Chemistry, Medical Oncology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Clin Chem. 2004 Nov;50(11):1986-93. doi: 10.1373/clinchem.2004.039149. Epub 2004 Sep 13.
Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.
Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].
High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant.
Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.
先前关于凋亡抑制因子survivin与乳腺癌患者预后相关性的定性研究结果相互矛盾。
采用定量TaqMan逆转录聚合酶链反应检测275例可手术切除肿瘤患者的乳腺癌组织中survivin mRNA,并将其与既定的临床病理因素、无复发生存期(RFS;102例事件)和总生存期(OS;81例事件)进行关联分析。
高survivin mRNA浓度主要见于年轻患者的组织和高级别癌组织中。高survivin浓度与雌激素受体或孕激素受体阴性肿瘤的相关性最强。在RFS的单因素Cox回归分析中,survivin浓度与预后不良显著相关,每增加10倍表达,风险比(HR)为1.99(95%置信区间,1.31 - 3.02;P = 0.001)。对于OS,发现survivin对预后不良有显著影响,HR为2.76(1.67 - 4.55;P <0.001)。进行了包括既定临床病理因素的多因素分析。对于RFS,年龄(P = 0.027)、淋巴结分类(P <0.001)和survivin [HR = 1.78(1.18 - 2.68);P = 0.006]对模型有显著贡献。对于OS,只有淋巴结分类(P <0.001)和survivin [HR = 3.05(1.83 - 5.10);P <0.001]具有显著性。
Survivin与预后不良呈现出强烈的、独立的相关性。Survivin可能用作一种新的标志物,对乳腺癌患者进行分层以采用更优化的治疗方式,或者它可能是一个有前景的新治疗靶点。