乳腺癌表达细胞周期蛋白依赖性激酶抑制物p27^(kip1)的预后意义  

Prognostic significance of cyclin dependent kinase inhibitor p27 kip1 expression in human breast cancer

作　　者：吴炅[1] 沈镇宙[1] 邵志敏[1] 

机构地区：[1]上海医科大学肿瘤医院胸外科分子生物实验室,200032

出　　处：《中华肿瘤杂志》1999年第4期265-268,共4页Chinese Journal of Oncology

基　　金：国家自然科学基金

摘　　要：目的　研究ｐ２７ｋｉｐ１ 在乳腺癌组织中的表达水平，及其与生物学行为的关系和对预后的作用。方法　以免疫组化法检测１８１ 例乳腺癌组织ｐ２７ｋｉｐ１ 蛋白表达水平，其中９１ 例进行了凋亡指数、凋亡相关蛋白ｂｃｌ２ 、ｂａｘ 的测定，另有１０６ 例检测了ｐ２１ＷＡＦ１／ＣＩＰ１ 、ｐ５３、ｍｄｍ２ 蛋白表达水平。结果　本组１８１ 例中，ｐ２７ｋｉｐ１ 蛋白阳性１２５ 例，占６９ ．１％ ；低表达者１２１ 例，占６６．９ ％ ；高表达者６０ 例，占３３．１ ％ 。乳腺癌组织ｐ２７ｋｉｐ１ 蛋白水平与病理组织学分级、癌周浸润程度、肿块大小、腋淋巴结转移情况、ＴＮＭ 分期、术后局部复发与转移均相关，与ｂｃｌ２ 、ｂａｘ、ｐ５３ 、ｐ２１ＷＡＦ１／ＣＩＰ１ 、ｍｄｍ２ 蛋白表达水平亦相关。单因素生存分析结果，ｐ２７ｋｉｐ１蛋白高表达组５ 年无病生存率９３ ．７％ 优于低表达组６４．７％ （ Ｐ＝ ０．０００１） 。Ｃｏｘ 模型多因素分析未显示ｐ２７ｋｉｐ１ 蛋白表达水平是独立的预后指标。结论　细胞周期蛋白依赖性激酶抑制剂（Ｃｋｉ）ｐ２７ｋｉｐ１ 在乳腺癌中具有一定预后价值；ｐ２７ｋｉｐ１ 不仅在细胞周期停滞中有作用。Objective To study the expression of p27 kip1 in breast cancer in relation to biological behavior and prognosis. Methods p27 kip1 expression at protein level was determined by immunohistochemistry technique in 181 patients with breast cancer. In addition, p27 WAF1/CIP1 , p53 and mdm 2 were examined in 106 cases of this series. Data about apoptotic index, bcl 2 and bax protein expression were available in the other 91 patients.Results Of the 181 patients, p27 kip1 expression was low in 121 (66.9%) and high in 60 (33.1%), respectively. p27 kip1 expression level was correlated with histological grade, tumor size, axillary lymph node status, post operative recurrence, invasion and metastasis. It was also correlated with bcl 2, bax, p53, p21 WAF1/CIP1 , and mdm 2 expression levels. Univariate analysis demonstrated better disease free survival in patients with higher p27 kip1 expression than in those with lower expression. However, by Cox multivariate analysis, p27 kip1 expression level was not found to be of independent prognostic significance. Conclusion As an inhibitor of cyclin dependent kinase, p27 kip1 favors prognosis of human breast cancer not only by arresting cell cycle in G 1 phase but also inducing cancer cell apoptosis.

关 键 词：乳腺癌 细胞周期蛋白 CKI 预后 

分 类 号：R737.9[医药卫生—肿瘤]