p16、Rb、CyclinD1和CDK4在EB病毒相关胃癌中的表达及其与预后的关系  

The expression of p16,Rb,CyclinD1 and CDK4 in Eepstein-Barr virus associated gastric carcinoma and its influence on prognosis

作　　者：赵小晓 陈健宁[1] 惠大阳[1] 潘宇航[1] 张志刚[1] 邵春奎[1] 

机构地区：[1]中山大学附属第三医院病理科,广州510630

出　　处：《新医学》2014年第9期586-592,共7页Journal of New Medicine

摘　　要：目的研究p16、视网膜母细胞瘤易感基因(Rb)、细胞周期蛋白D1(CyclinD1)和周期蛋白依赖性激酶4(CDK4)在EB病毒相关胃癌(EBVaGC)组织中的表达及其对EBVaGC预后的影响。方法对1 545例胃癌标本采用组织芯片和EBV编码小RNA(EBER)原位杂交的方法筛选EBVaGC,并在EBV阴性胃癌(EBVnGC)中随机选取366例作为阴性对照,用组织芯片和免疫组织化学染色的方法检测p16、Rb、CyclinD1和CDK4在EBVaGC与EBVnGC中的表达,并分析p16、Rb、CyclinD1和CDK4与EBVaGC临床病理及预后的关系。结果 1 545例胃癌标本中,92例EBER阳性,p16、Rb、CyclinD1和CDK4在EBVaGC中的阳性例数分别为0例(0%)、64例(70%)、28例(30%)、63例(68%),p16、Rb、CyclinD1和CDK4在EBVnGC中的阳性例数分别为78例(21%)、224例(61%)、42例(12%)、264例(72%),p16与CyclinD1在EBVaGC和EBVnGC中的表达率比较差异均有统计学意义(P均<0.01),Rb与CDK4在EBVaGC和EBVnGC中的阳性表达率比较差异无统计学意义(P>0.05)。在EBVaGC中,Rb与CyclinD1表达呈正相关(r=0.332,P=0.003)。CyclinD1与EBVaGC患者的年龄相关(P<0.05),CDK4与EBVaGC患者的日本分型和肿瘤发生部位相关(P<0.05)。单因素分析显示,EBVaGC的Lauren分型和CyclinD1的表达影响胃癌患者预后(P<0.05);多因素分析表明,CyclinD1是EBVaGC独立的预后指标(P<0.05)。结论 CyclinD1是EBVaGC独立的预后影响因子,CyclinD1蛋白阳性表达的EBVaGC患者预后较好。Objective To detect the expression of p16,CyclinD1,CDK4 and Rb in EBVaGC,explore their relationship with clinical pathological factors and analyze their influence on prognosis. Methods Samples from 1545 gastric carcinoma patients undergoing gastrectomy were collected for tissue microarray and EBER in situ hybridization to screen EBVaGC. Among these EBVnGC samples,366 were randomly selected as negative controls. Expression of p16,CyclinD1,CDK4 and Rb in EBVaGC and EBVnGC samples was detected by imunohistochemistry and their association with clinopathological factors and clinical prognosis of EBVaGC was analyzed. Results Among 1545 patients with gastric cancer,92 were positive for EBER. The number of EBVaGC patients expressing p16,CyclinD1,CDK4 and Rb was 0（ 0%）,28（ 30%）,63（ 68%） and 64（ 70%）. The percentage of positive expression of p16,CyclinD1,CDK4 and Rb in EBVnGC patients was 0%（ 78 of 366）,12%（ 42 of 366）,72%（ 264 of 366） and 61%（ 224 of 366）. The expression of p16 and CyclinD1 proteins significantly differed between two groups（ P〈0. 01）. The expression of Rb and CyclinD1 did not differ between two groups（ P〉0. 05）. For EBVaGC patients,the expression of Rb was positively associated with CyclinD1（ r = 0. 332,P = 0. 003） and the expression of CyclinD1 was significantly correlated with age（ P〈0. 05）. In addition,CDK4 expression was significantly correlated with Japanese classification and tumor location（ both P〈0. 05）. Univariate analysis revealed that both CyclinD1 expression and Lauren classification were significantly associated with better overall survival in EBVaGC patients（ both P〈0. 05）. Multivariate analysis showed that CyclinD1 expression was an independent prognostic factor in EBVaGC patients（ P〈0. 05）. Conclusion CyclinD1 expression is an independent prognostic factor in EBVaGC. EBVaGC patients with positive expression of CyclinD1 protein has better prognosis.

关 键 词：胃癌 P16 视网膜母细胞瘤易感基因 细胞周期蛋白D1 周期蛋白依赖性激酶4 表达 预后 

分 类 号：R735.2[医药卫生—肿瘤]