口腔鳞状细胞癌细胞周期因子p27 cyclin D1及CDK4的表达与意义

目的：从细胞周期调控的角度来探讨口腔鳞状细胞癌（OSCC）的发生、发展及预后和p27、cyclin D1和CDK4的关系。方法：采用免疫组织化学方法，检测了50例口腔鳞状细胞癌及10例正常口腔粘膜中p27、cyclinD1和CDK4蛋白表达的水平，然后用Spearman 相关分析检查它们与临床病理学指标的关系以及它们三者之间的相关关系，用Kaplan-Meier方法绘制生存曲线并进行生存分析，Cox比例风险模型作预后分析。结果：1)p27在所有正常口腔粘膜上皮均呈现高表达，而在口腔鳞状细胞癌组织表达降低，p27的低表达与临床分期，淋巴结转移有显著性相关关系，cyclin D1和CDK4在正常粘膜上皮呈现低水平表达，在口腔钙状细胞癌组织中过表达。2)cyclinD1和CDK4在正常粘膜上皮呈现低水平表达，在口腔鳞状细胞癌组织中过表达.2)cyclin D1的表达与CDK4呈正相关（r=0.442,P=0.001）;p27与CDK4的表达呈负相关（r=-0.384,P=0.006）.3)Kaplan-Meier生存分析显示p27高表达组（ ）的各期的生存均高于低表达组（-）,cyclin D1染色（ ）组的生存率低于（-）组。4）Cox比例风险模型分析结果显示p27蛋白表达水平，cyclinD1蛋白表达水平，淋巴结转移和临床分期分别是口腔鳞状细胞癌的独立预后指标。结论：口腔鳞状细胞癌组织中，p27,cyclin D1和CDK4蛋白的异常表达说明它们均参与了口腔鳞状细胞癌的发生发展，且在这一过程中三者之间存在相互协同与制约关系。在临床应用中有可能将p27和cyclin D1蛋白的表达程度作为判断口腔鳞状癌患者预后的指标。

Expression and Prognostic Significance of Cell Cycle Regulator p27、Cyclin D1 and CDK4 in Oral Squamous Cell Carcinoma

Objective:To investigate the role of t he cell cycle regulators cyclin D1?cy-clin-dependent kinase(CDK4)and cyclin-dep endent kinase inhibitors(p27 kip1 )in oncogenesis and development of oral squamous cell carcinomas(OSCC). Methods:The expression of cyclin D1?CDK4and p27 kip1 in50OSCC specimens was detected by immunohistochemical method.The re-lat ionship between them and clinicopathological characteristics or survival time w as analysis by Spearman correlation test or Kaplan-Meier method,respectively, while multivariate prognostic analyses were performed by using Cox propotional h azards model.Results:1)In the normal o-ral epithelium,cells showed strongl y positive,while in OSCC showed p27reduced expression.Low p27expression in OSCC was significantly associated with late TNM stage,high incidence of lymph node metastasis.Cyclin D1and CDK4showed low expression in normal oral epithel ium while over-expression in OSCC.2)Not only between overexpression of cycli n D1and CDK4but also be-tween expression of p27and CDK4showed significant ly correlation,while expression of p27did not correlated with expression of cyclin D1.3)Kaplan-Meier analysis sho wing that the cumula-tive survival for patients with high p27 kip1 expression is significantly higher than that of the low p27 kip1 expression group(P=0.046,by the log-rank test),the cumulative sur vival for patients with tumors of cyclin D1(+)was significantly higher than that for patients with tumors of cyclin D1(-)(P=0.042,by the Log ran k test).4)Multivariate analysis was performed using the Cox model.In the an alysis,expression of p27and cyclin D1,stage and lymphnode metestasis were r ecognized as indepent prognostic factors.Conclusion:Abnormal expression of p 27?cyclin D1and CDK4indi-cates that they was invovled in oral carcinogenes is.The correlation relationship between the ex-pression of p27?cyclin D1an d CDK4suggested that inappopriate coexpression of p27?cyclin D1and CDK4may raect on the oncogenesis and development of OSCC.The reduced expression of p 27and overexpression of protein cyclin D1might be useful indicators of prog nosis.