Sieuwerts Anieta M, Look Maxime P, Meijer-van Gelder Marion E, Timmermans Mieke, Trapman Anita M A C, Garcia Roberto Rodriguez, Arnold Miranda, Goedheer Anneke J W, de Weerd Vanja, Portengen Henk, Klijn Jan G M, Foekens John A
Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands.
Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3319-28. doi: 10.1158/1078-0432.CCR-06-0225.
To evaluate the prognostic value of cyclin E with a quantitative method for lymph node-negative primary breast cancer patients.
mRNA transcripts of full-length and splice variants of cyclin E1 (CCNE1) and cyclin E2 (CCNE2) were measured by real-time PCR in frozen tumor samples from 635 lymph node-negative breast cancer patients who had not received neoadjuvant or adjuvant systemic therapy.
None of the PCR assays designed for the specific splice variants of the cyclins gave additional prognosis-related information compared with the common assays able to detect all variants. In Cox multivariate analysis, corrected for the traditional prognostic factors, high levels of cyclin E were independently associated with a short distant metastasis-free survival [hazard ratio (HR), 3.40; P < 0.001 for CCNE1 and HR, 1.76; P < 0.001 for CCNE2, respectively]. After dichotomizing the tumors at the median level of 70% tumor cells, the multivariate analysis showed particularly strong results for CCNE1 in the group of 433 patients with stroma-enriched primary tumors (HR, 5.12; P < 0.001). In these tumors, the worst prognosis was found for patients with estrogen receptor-negative tumors expressing high CCNE1 (HR, 9.89; P < 0.001) and for patients with small (T1) tumors expressing high CCNE1 (HR, 8.47; P < 0.001).
Our study shows that both CCNE1 and CCNE2 qualify as independent prognostic markers for lymph node-negative breast cancer patients, and that CCNE1 may provide additional information for specific subgroups of patients.
采用定量方法评估细胞周期蛋白E对淋巴结阴性原发性乳腺癌患者的预后价值。
通过实时聚合酶链反应（PCR）检测635例未接受新辅助或辅助全身治疗的淋巴结阴性乳腺癌患者冷冻肿瘤样本中细胞周期蛋白E1（CCNE1）和细胞周期蛋白E2（CCNE2）的全长及剪接变体的信使核糖核酸转录本。
与能够检测所有变体的常规检测方法相比，针对细胞周期蛋白特定剪接变体设计的PCR检测均未提供额外的预后相关信息。在经传统预后因素校正的Cox多变量分析中，细胞周期蛋白E水平高与远处无转移生存期短独立相关[风险比（HR），3.40；CCNE1的P<0.001，CCNE2的HR为1.76，P<0.001]。在将肿瘤细胞中位数水平设定为70%进行二分法分析后，多变量分析显示，在433例富含基质原发性肿瘤患者组中，CCNE1的结果尤为显著（HR，5.12；P<0.001）。在这些肿瘤中，雌激素受体阴性且CCNE1表达高的患者（HR，9.89；P<0.001）以及肿瘤较小（T1）且CCNE1表达高的患者（HR，8.47；P<0.001）预后最差。
我们的研究表明，CCNE1和CCNE2均有资格作为淋巴结阴性乳腺癌患者的独立预后标志物，且CCNE1可能为特定亚组患者提供额外信息。
