广州地区EB病毒相关胃癌的临床病理特征及相关分子表达

目的 观察鼻咽癌高发区广州地区EB病毒相关胃癌的构成比、临床病理特征、EB病毒的潜伏类型,并初步探讨DNMT1、p16和cyclin D1在发病过程中的作用.方法 对676例胃癌采用组织芯片和EBER1原位杂交的方法筛选EB病毒相关胃癌,并用免疫组织化学EnVision法检测EB病毒潜伏期膜蛋白(LMP)和DNMT1、p16和cyclin D1的表达.结果 在676例胃癌中,45例EB病毒阳性(6.7%),EB病毒相关胃癌以男性为主,主要发生在胃的中上2/3,以弥漫型多见(P＜0.05).EBNA1和LMP2A的阳性例数分别为42例(93.3%)和24例(53.3%),EBNA2、LMP1和ZEBRA均未见表达.DNMT1、p16和cyclin D1在45例EB病毒相关胃癌的阳性例数分别为35例(77.8%)、10例(22.2%)和29例(64.4%),在40例EB病毒阴性胃癌的阳性例数分别为20例(50.0%)、25例(62.5%)和12例(30.0%),3个分子在两组胃癌的表达率差异均具有统计学意义(P＜0.05).p16与肿瘤的浸润深度有关(P＜0.05).LMP2A与DNMT1、DNMT1与p16、p16与cyclin D1存在相关关系(P＜0.05).结论 广州地区EB病毒相关胃癌占胃癌构成比的6.7%(45/676),EB病毒的潜伏类型部分为Ⅰ型,部分介于Ⅰ型和Ⅱ型之间.LMP2A、DNMT1、p16和cyclin D1的相互作用在EB病毒相关胃癌发生过程中起着重要的作用.

Clinicopathologic features and protein expression study of Epstein-Barr virus-associated gastric carcinoma in Guangzhou

Objective To investigate the prevalence of Epstein-Barr virus (EBV) -associated gastric carcinomas in Guangzhou, their clinicopathologic features and related protein expressions including DNMT1,p16, and cyclin D1. Method A total of 676 cases of EBV-associated gastric carcinoma were included in the study. The presence of EBV-encoded small RNA1 (EBER1), a marker for EBV infection, was analyzed by in-situ hybridization using formalin-fixed and paraffin-embedded tumor samples. Expression of EBV-encoded proteins, DNMT1, p16 and cyclin D1 were detected by immunohistochemistry. Results Forty-five of 676 gastric carcinomas showed EBER intranuclear positivity in all tumor cells. EBV involvement was significantly more frequent among the male than the female patients, especially in tumors of less differentiated types ( diffuse type) and involving the upper stomach (P ＜ 0. 05 ). EBNA1 and LMP2A expression were detected in 42 (93. 3% ) and 24(53. 3% ) cases, respectively. None expressed EBNA2,LMP1, and ZEBRA. Among 45 cases of EBV associated gastric carcinomas, DNMT1, p16 and cyclin D1 expression were seen in 35 ( 77. 8% ), 10 ( 22. 2% ), and 29 ( 64.4% ) cases, respectively. In contrast,among 40 EBV negative gastric carcinomas, expression of the three proteins were 20 (50. 0% ), 25 (62. 5% ) and 12(30. 0% ), respectively. The difference of expression of the three proteins between the two groups was significant ( P ＜ 0. 05 ). Expression of p16 correlated with the depth of the tumor invasion.Correlated protein expression was seen between LMP2A and DNMT1, between DNMT1 and p16, and between p16 and cyclin D1 ( P ＜ 0. 05 ). Conclusions EBV associated gastric carcinoma accounts for 6. 7% of gastric carcinomas in Guangzhou with the Latency I pattern in some cases and between Latency Ⅰ and Ⅱ in others. The correlated expression of LMP2A, DNMT1, p16 and cyclin D1 may contribute to the pathogenesis of EBV associated gastric carcinomas.