细胞周期相关蛋白CyclinD1、CDK4、p16在大肠癌中的表达及其意义

Clinicopathological significance of the expression of CyclinD1,CDK4 and p16 in the colorectal carcinoma

目的探讨细胞周期调控因子在大肠癌中的表达及其与大肠癌临床病理特征的关系。方法应用免疫组化S-P法对70例大肠癌组织及距癌灶3 cm以外的癌旁组织,10 cm以外的正常组织中CyclinD1、CDK4、和p16进行检测。结果CyclinD1和CDK4在大肠癌中过度表达,分别为36/70(51.4%)和28/70(40.0%),并与肿瘤的分化程度呈反比,有淋巴结转移的大肠癌,其CyclinD1和CDK4的阳性率分别为70.0%和60.0%,无淋巴结转移的大肠癌阳性率分别为44.0%和32.0%,两者相比差异有显著性(P(0.05),p16在大肠癌中为低表达33/70(47.1%),癌旁组织和正常组织中p16的表达分别为57.1%和71.4%,CyclinD1与CDK4呈正相关关系(P(0.05)。CyclinD1与p16呈负相关关系(P(0.05)。结论CyclinD1、CDK4的过度表达与肿瘤的分化程度、淋巴结转移密切相关;CyclinD1的过度表达和p16的低表达在大肠癌发生中起协同作用;大肠癌的发生机制涉及CyclinD1、CDK4和p16调节环路中多个基因的异常。

Objective To investigate the relationship between the expression of CyclinD1, CDK4 and p16 and clinical pathological characteristics in colorectal carcinoma. Methods CyclinD1, CDK4 and p16 were detected in 70 colorectal carcinomas,adjacent tissues of colorectal carcinoma and normal tissues by immunohistochemical method. Results Overexpression of CyclinD1 and CDK4 revealed in 36/70 samples （51.4%） and 28/70 samples （40.0%） respectively, which showed a negative correlation with tumor differentiation （P 〈 0.01）. The expression percent of CyclinD1 and CDK4 were 70.0% and 60.0% respectively in metastatic cancer whereas only 44.0% of CyclinD1 and 32.0% of CDK4 expression were shown in non-metastatic cancer. The over expression rate of CyclinD1 and CDK4 in cancer tissues were significantly higher than that in tumor-adjacent and normal tissues （P 〈0.05）. The positive rates of p16 were 47.1% in samples of colorectal carcinomas. The incidence of p16 was significantly lower in cancer tissues than that in normal tissues（P 〈 0.01）. There is a positive relationship between CyclinD1 and CDK4 （P 〈 0.05）. There is a negative relationship between p16 and CyclinD1 in this samples （P 〈 0.05）. Conclusions Over expression of CyclinD1 and CDK4 exsist in colorectal carcinoma and show a good relation with tumor differentiation and lymphnode metastasis, Both the over expression of CyclinD1 and the lower expression of p16 coexist in the development of colorectal carcinoma. Abnormality of many genes in the regulatory pathway of CyclinD1, CDK4 and p16 maybe involved in the molecular mechanism of colorectal carcinogenesis.