Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer
Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer
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DOI：
10.1200/jco.2003.04.121
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发表时间：
2003-12-01
影响因子：
45.3
通讯作者：
Coleman, N
中科院分区：
文献类型：
--
作者：
Gonzalez, MA;Pinder, SE;Coleman, N
目的：以微小染色体维持蛋白(MCM)的表达为例，验证乳腺癌预后信息可能来源于准确评估上皮细胞周期进入的假说。材料与方法：应用免疫组织化学方法检测MCM-2在乳腺组织中的分布。根据对67个完整组织切片的初步研究，能量计算导致选择了一个独立的347个核心乳腺癌组织微阵列验证集。结果：MCM-2在正常乳腺(P=.0003)和乳腺癌(P<；.0001)全组织切片中的表达明显高于标准增殖标记物Ki-67。在221个可评估的浸润性癌核心中，MCM-2LI与肿瘤大小(P=.002)、核分裂指数(P<；.0001)、组织学分级(P<；.0001)和诺丁汉预后指数(NPI)评分(P<；.0001)呈正相关。以50%为临界值，MCM-2LI与总生存期(P=.0007)、无病间期(P=.0002)、区域复发(P=.011)和远处转移(P=.0016)相关。COX回归分析显示MCM-2LI是一个独立于组织学分级、淋巴结分期和Ki-67LI的乳腺癌预后因子，而不是NPI评分。结论：MCM-2可以作为乳腺癌预后预测的有用指标，例如结合目前NPI中使用的参数。(C)2003年，由美国临床肿瘤学会提供。
Purpose: To test the hypothesis that prognostic information in breast cancer may be derived from an accurate assessment of epithelial cell cycle entry, as indicated by expression of minichromosome maintenance (MCM) proteins.Materials and Methods: We used immunohistochemistry to examine the distribution of Mcm-2 in breast tissue. Power calculations based on a pilot study of 67 whole tissue sections led to selection of an independent 347-core breast carcinoma tissue microarray validation set. We tested for associations between Mcm-2 (and Ki-67) labeling index (LI) and various clinicopathologic parameters.Results: Mcm-2 was expressed more frequently than the standard proliferation marker Ki-67 in whole tissue sections of normal breast (P = .0003) and breast carcinoma (P < .0001). In 221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive association with tumor size (P = .002), mitotic index (P < .0001), histologic grade (P < .0001), and the Nottingham Prognostic Index (NPI) score (P < .0001). Using a cutoff value of 50%, Mcm-2 LI was associated with overall survival (P = .0007), disease-free interval (P = .0002), and with the development of regional recurrence (P = .011) and distant metastases (P = .0016). Cox regression analysis suggested that the Mcm-2 LI is a strong prognostic factor in breast cancer that is independent and superior to histologic grade, lymph node stage, and Ki-67 LI, but not the NPI score.Conclusion: Mcm-2 may be of utility as a prognostic marker to refine the prediction of outcome in breast cancer, for example when combined with parameters currently used in the NPI. (C) 2003 by American Society of Clinical Oncology.