CAJ | 학술논문

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1545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1545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。
목적：연구 p16、시망막모세포류역감기인（Rb）、세포주기단백 D1（CyclinD1）화주기단백의뢰성격매4（CDK4）재 EB 병독상관위암（EBVaGC）조직중적표체급기대 EBVaGC 예후적영향。방법대1545례위암표본채용조직심편화 EBV 편마소 RNA （EBER）원위잡교적방법사선EBVaGC，병재 EBV 음성위암（EBVnGC）중수궤선취366례작위음성대조，용조직심편화면역조직화학염색적방법검측 p16、Rb、CyclinD1화 CDK4재 EBVaGC 여 EBVnGC 중적표체，병분석 p16、Rb、CyclinD1화 CDK4여 EBVaGC 림상병리급예후적관계。결과1545례위암표본중，92례 EBER 양성， p16、Rb、CyclinD1화 CDK4재 EBVaGC 중적양성례수분별위0례（0％）、64례（70％）、28례（30％）、63례（68％），p16、Rb、CyclinD1화 CDK4재 EBVnGC 중적양성례수분별위78례（21％）、224례（61％）、42례（12％）、264례（72％），p16여 CyclinD1재 EBVaGC 화 EBVnGC 중적표체솔비교차이균유통계학의의（P 균＜0.01），Rb 여 CDK4재 EBVaGC 화 EBVnGC 중적양성표체솔비교차이무통계학의의（P ＞0.05）。재 EBVaGC 중，Rb 여 CyclinD1표체정정상관（r ＝0.332，P ＝0.003）。CyclinD1여 EBVaGC 환자적년령상관（P ＜0.05），CDK4여 EBVaGC 환자적일본분형화종류발생부위상관（P ＜0.05）。단인소분석현시，EBVaGC 적 Lauren 분형화 CyclinD1적표체영향위암환자예후（P＜0.05）；다인소분석표명，CyclinD1시 EBVaGC 독립적예후지표（P ＜0.05）。결론CyclinD1시EBVaGC 독립적예후영향인자，CyclinD1단백양성표체적 EBVaGC 환자예후교호。
Objective To detect the expression of p1 6,CyclinD1 ,CDK4 and Rb in EBVaGC,ex-plore their relationship with clinical pathological factors and analyze their influence on prognosis.Methods Samples from 1 545 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 p1 6,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 1 545 patients with gastric cancer,92 were positive for EBER.The number of EBVaGC patients expressing p1 6,CyclinD1 ,CDK4 and Rb was 0 (0%),28 (30%),63 (68%)and 64 (70%).The percentage of positive expression of p1 6,CyclinD1 ,CDK4 and Rb in EBVnGC patients was 0%(78 of 366),1 2% (42 of 366),72% (264 of 366)and 61 % (224 of 366).The expression of p1 6 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 asso-ciated 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 classi-fication were significantly associated with better overall survival in EBVaGC patients (both P <0.05).Multiva-riate 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.