Which cyclin E prevails as prognostic marker for breast cancer? Results from a retrospective study involving 635 lymph node-negative breast cancer patients
Which cyclin E prevails as prognostic marker for breast cancer? Results from a retrospective study involving 635 lymph node-negative breast cancer patients
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DOI：
10.1158/1078-0432.ccr-06-0225
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发表时间：
2006-06-01
影响因子：
11.5
通讯作者：
Foekens, JA
中科院分区：
文献类型：
--
作者：
Sieuwerts, AM;Look, MP;Foekens, JA
目的：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。患者和方法：通过实时PCR测量来自635名未接受新辅助或辅助全身治疗的淋巴结阴性乳腺癌患者的冷冻肿瘤样本中细胞周期蛋白E1（CCNE1）和细胞周期蛋白E2（CCNE2）的全长和剪接变体的mRNA转录物。结果：没有任何PCR检测结果与能够检测所有变体的常见测定相比，针对细胞周期蛋白的特定剪接变体设计的方法提供了额外的预后相关信息。在 Cox 多变量分析中，校正了传统的预后因素后，高水平的细胞周期蛋白 E 与较短的无远处转移生存期独立相关[风险比 (HR)，3.40； CCNE1 和 HR 的 P < 0.001，1.76； CCNE2 的 P < 0.001，分别]。在以 70% 肿瘤细胞的中位水平对肿瘤进行二分后，多变量分析显示，CCNE1 在 433 名富含基质的原发肿瘤患者组中显示出特别强的结果（HR，5.12；P < 0.001）。在这些肿瘤中，高表达 CCNE1 的雌激素受体阴性肿瘤患者（HR，9.89；P < 0.001）和高表达 CCNE1 的小（T-1）肿瘤患者（HR，8.47；P < 0.001）预后最差。结论：我们的研究表明，CCNE1 和 CCNE2 都有资格作为淋巴结阴性乳腺癌患者的独立预后标志物，CCNE1 可能提供针对特定患者亚组的附加信息。
Purpose: To evaluate the prognostic value of cyclin E with a quantitative method for lymph node - negative primary breast cancer patients.Patients and Methods: mRNA transcripts of full-length and splice variants of cyclin El (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.Results: 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 (T-1) tumors expressing high CCNE1 (HR, 8.47; P < 0.001).Conclusion: 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.