Expression of p27kip I in breast cancer and its prognostic significance
Expression of p27kip I in breast cancer and its prognostic significance
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DOI：
10.1002/path.1464
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发表时间：
2003-11-01
影响因子：
7.3
通讯作者：
Ellis, IO
中科院分区：
文献类型：
--
作者：
Barnes, A;Pinder, SE;Ellis, IO
p27kip1 是细胞周期蛋白依赖性激酶抑制剂 KIP/CIP 家族的成员，是一种负性细胞周期调节因子，被认为在肿瘤抑制中发挥作用。在许多人类癌症中观察到这种蛋白质的水平降低。然而，关于 p27kip1 是否在乳腺癌中发挥作用（包括预测行为和预后）的证据是相互矛盾的。本研究旨在对 830 例乳腺癌病例进行一项明确的研究，对患者进行中位随访 104 个月，以确定真正的预后意义（如果有的话）。使用组织微阵列的免疫组织化学分析和三种评分方法来评估 p27kip1 表达。单变量分析显示 p27kip1 表达减少与肿瘤分级增加、核多形性、有丝分裂和肾小管形成减少之间存在显着关系（所有 p < 0.001）。还观察到 p27 减少、雌激素受体阴性状态和导管/非特殊类型肿瘤之间存在显着关联。生存分析表明，与 p27kip1 低表达的癌症患者相比，p27kip1 水平高的肿瘤患者的生存期有所改善。然而，在多变量分析中，与现有因素相比，p27kip1 并不是独立的预后因素。结论是，p27kip1 水平与组织学分级和个体分级成分之间的负相关关系表明 p27kip1 在细胞增殖和分化中发挥作用，但在临床上没有用处。版权所有 (C) 2003 John Wiley Sons, Ltd.
p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors and is a negative cell-cycle regulator that is thought to play a role in tumour suppression. Reduced levels of this protein have been observed in a number of human cancers. However, evidence is conflicting as to whether p27kip1 has a role to play in breast cancer, including predicting behaviour and prognosis. The present investigation aimed to provide a definitive study of 830 breast cancer cases with median patient follow-up of 104 months to determine the true prognostic significance, if any. Immunohistochemical analysis of tissue microarrays and three scoring methods were used to assess p27kip1 expression. Univariate analysis showed a significant relationship between reduced p27kip1 expression and increasing tumour grade, nuclear pleomorphism, mitosis, and decreasing tubule formation (all p < 0.001). Significant associations between reduced p27, negative oestrogen receptor status, and ductal/no special type tumours were also observed. Survival analysis demonstrated that patients with tumours with high p27kip1 levels had an improved survival compared with those with cancers with low expression. On multivariate analysis, when compared with existing factors, p27kip1 was not, however, an independent prognostic factor. It is concluded that the inverse relationship between p27kip1 levels and histological grade and individual grade components suggests a role for p27kip1 in both cell proliferation and differentiation, but is not clinically useful. Copyright (C) 2003 John Wiley Sons, Ltd.