【摘要】 目的探讨细胞周期调控因子Cyclin D1、CDK4、P16蛋白及p16基因表达与大肠癌的临床病理特征及预后的关系。方法应用免疫组织化学SP法检测12例正常大肠黏膜和89例大肠癌组织中Cyclin D1、CDK4、P16蛋白的表达并进行术后随访,对其中40例大肠癌组织进行p16基因SSCP-PCR分析,评估Cyclin D1、CDK4、P16蛋白及p16基因表达与大肠癌组织学分级、临床Dukes分期、淋巴结转移及术后生存率的关系。结果大肠癌组织Cyclin D1蛋白阳性标记位于癌细胞核,P16和CDK4位于细胞浆和细胞核,正常大肠黏膜未见Cyclin D1表达,P16和CDK4仅在细胞浆内表达。大肠癌组织中Cylin D1表达率为42.69％;P16胞浆表达率为57.30％,其中同时有核表达者为47.19％;CDK4胞浆表达率为92.13％,其中同时有核表达者为24.72％。正常大肠黏膜P16和CDK4表达率分别为25.00％和41.66％,明显低于大肠癌组织的表达(P<0.05)。大肠癌组织Cyclin D1表达与淋巴结转移、患者术后生存率有明显的关系(P<0.05),与临床分期、组织学分级相关性不显著(P>0.05)。CDK4核表达与组织学分级有关(P<0.05),与临床分期和淋巴结转移及生存率的相关性不显著(P>0.05)。CDK4胞浆表达、P16胞浆表达和P16核表达与临床分期、组织学分级、淋巴结转移及生存率的相关性不显著。Cyclin D1、CDK4、P16三者在核区阳性表达有相关性。p16基因缺失率为47.50％,与组织学分级有关(P<0.05),p16基因与P16蛋白表达呈正相关(P<0.05)。结论大肠癌组织Cyclin D1阳性表达与淋巴结转移关系密切,提示患者的预后较差,尤其对Dukes B期患者的预后评估有重要意义。大肠癌细胞分化程度与p16基因缺失及CDK4核阳性表达有一定关系。细胞周期调控因子Cyclin D1/CDK4/P16对细胞的异常调控可能是发生大肠癌的原因之一。更多还原

【Abstract】 Objective To detect the correlation of cell cycle regulation factors Cyclin D1, CDK4, P16 protein and p16 gene expression with clinicopathologic features and prognosis in colorectal carcinoma. Methods The expression of Cyclin D1, CDK4 and P16 protein were examined with SP immunohistochemical technique in 89 cases of colorectal carcinoma and 12 cases of normal colorectal tissues, p16 gene was detected with SSCP-PCR technique in 40 cases of colorectal carcinoma. The relationship was analyzed among the Cyclin D1, CDK4, P16 protein and p16 gene expression with clinical stage, pathological grade, lymph node metastasis and survival rate of patients with colorectal carcinoma. Results The positive staining was located at nucleus for Cyclin D1, cytoplasm and nucleus for P16 and CDK4 in colorectal carcinoma. The positive staining was only located within cytoplasm for P16 and CDK4, and no positive staining for Cyclin D1 in normal colorectal tissues. In colerectal carcinomas, the expression rate of Cyclin D1 was 42.69％ in uncleus, P16 was 57.30％ in cytoplasm and 47.19％ in uncleus, CDK4 was 92.13％ in cytoplasm, and 22.72％ in uncleus, The expression rate of P16 and CDK4 was 25.00％ and 41.66％ in normal colorectal tissues respectively, and significantly lower than that in colerectal carcinoma (P<0.05). The expression of Cyclin D1 was found a significant association with lymph node metastasis and survival rates (P<0.05), but no relationship with clinical stage, pathological grade (P>0.05). The expression of CDK4 in nucleus was correlated with pathological grade (P<0.05), but no relationship with clinical stage, lymph node metastases and survival rate (P>0.05). The expression of CDK4 and P16 in cytoplasm and P16 in nucleus was not shown significant association with clinical stage, pathological grade, lymph node metastases and survival rate. Furthermore, significant associations was found between Cyclin D1, P16 and CDK4 expression in nucleus. In addition, p16 gene deletion rate was 47.50％. It has close relation with histological classification (P<0.05). There was a positive correlation in expression of p16 gene with P16 protin (P<0.05). Conclusions Cyclin D1 is a prognostic indicating tool in colerectal carcinoma, especially in stage Ⅱ. In some extent, the p16 gene detection and CDK4 nuclear expressions are closely associated with cell differentiation. The abnormal regulation of Cyclin D1/CDK4/P16 factors may be one of the causes of colorectal carcinoma.更多还原