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CyclinD1、p21^(WAF1)、p53及Ki-67在肝细胞癌中的表达及与预后的关系 被引量:16

Expression of cyclin D1,p21^(WAF1),p53 and Ki-67 in hepatocellular carcinoma:a pathological study
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摘要 目的探讨肝细胞癌(HCC)中cyclin D1、p21、p53及Ki-67蛋白的表达及其与HCC预后的关系。方法选择2000年1月-2005年1月在解放军总医院行手术切除的80例HCC患者的肝组织标本,采用EliVision法进行cyclin D1、p21WAF1、p53及Ki-67免疫组化染色,分析其表达水平与HCC病理特征的关系,并进行生存分析。结果 Cyclin D1、p21WAF1、p53及Ki-67在HCC中的阳性表达率分别为38.8%、40.5%、65.4%及80.0%,均明显高于癌旁肝组织(分别为19.0%、11.5%、0.0%、6.3%,P<0.005)。相关分析显示,cyclin D1阳性表达与核分级呈正相关(P=0.041),p21WAF1及p53阳性表达与肿瘤分化程度(P=0.032、P=0.031)和血管浸润(P=0.036、P=0.011)呈正相关,Ki-67阳性表达与肿瘤分化程度(P=0.004)、核分级(P=0.045)和血管浸润(P=0.001)呈正相关。生存分析显示,cyclin D1及Ki-67高表达者预后较差。Ki-67阳性表达与p53(P=0.000)及p21WAF1(P=0.047)阳性表达有明显相关性,其他各蛋白之间表达无明显相关。Cox回归模型分析显示,肿瘤大小(P=0.042)、肿瘤数目(P=0.004)及血管浸润(P=0.000)为HCC的独立预后因素。结论 Cyclin D1、p21WAF1、p53及Ki-67可能参与了HCC的生物学进程;cyclin D1及Ki-67阳性表达对HCC预后的判断有一定价值。 Objective To explore the expression of cyclin D1, p21wAF1, p53 and Ki-67 protein in hepatocellular carcinoma (HCC) and its relationship with prognosis of HCC patients. Methods Liver specimens were collected from 80 HCC patients who received hepatectomy in the General Hospital of PLA from Jan. 2000 to Jan. 2005, and the expressions of cyclin D1, p21wAFt, p53 and Ki-67 protein were determined by immunohistochemical staining (EliVision method) to investigate the relationship between the protein expressions and the clinicopathologic characteristics of HCC, and their relationship with the survival rate of the patients was analyzed. Results The positive expression rates of cyclin D1, p21wAFI, p53 and Ki-67 in HCC were 38.8%, 40.5%, 65.4% and 80.0% respectively, and they were significantly higher than those in matched normal tissues (19.0%, 11.5%, 0.0% and 6.3% respectively, P〈0.00S). Correlation analysis showed that the expression of cyclin D1 was positively related to the nuclear grade (P=0.041), the expression of p21wAH and p53 were positively related to the tumor differentiation (P=0.032, P=0.031) and vascular invasion (P=0.036, P=0.011), the expression of Ki-67 was positively related to the tumor differentiation (P=0.004), nuclear grade (P=0.045) and vascular invasion (P=0.001). Survival analysis showed the prognosis was poor in patients with high expression of cyclin D1 or/and Ki-67. The expression of Ki-67 was significantly related to the expression of p53 (P=0.000) and p21wAF1 (P=0.047), but no significant relation was found among the expression of other proteins. Cox regression analysis showed that the tumor size (P=0.042), tumor number (P=0.004) and vascular invasion (P=0.000) were independent prognostic factors of HCC. Conclusions The cyclin D 1, p21wAF1, p53 and Ki-67 protein may be involved in the biological process of HCC. The positive expression of cyclin D 1 and Ki- 67 may be used to evaluate the prognosis of patients with HCC.
出处 《解放军医学杂志》 CAS CSCD 北大核心 2014年第1期20-24,共5页 Medical Journal of Chinese People's Liberation Army
基金 国家“十二五”重大专项(2012ZX10002003-004-006) 军队临床高新技术项目(2010jxgs099)~~
关键词 肝细胞 细胞周期蛋白D1 周期素依赖激酶抑制剂p21 肿瘤抑制蛋白质P53 KI-67抗原 carcinoma, hepatocellular cyclin D1 cyclin-dependent kinase inhibitor p21 tumor suppressor protein p53 Ki-67 antigen
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