CAJ | 학술논문

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.
목적 관찰비인암고발구엄주지구EB병독상관위암적구성비、림상병리특정、EB병독적잠복류형,병초보탐토DNMT1、p16화cyclin D1재발병과정중적작용.방법 대676례위암채용조직심편화EBER1원위잡교적방법사선EB병독상관위암,병용면역조직화학EnVision법검측EB병독잠복기막단백(LMP)화DNMT1、p16화cyclin D1적표체.결과 재676례위암중,45례EB병독양성(6.7%),EB병독상관위암이남성위주,주요발생재위적중상2/3,이미만형다견(P＜0.05).EBNA1화LMP2A적양성례수분별위42례(93.3%)화24례(53.3%),EBNA2、LMP1화ZEBRA균미견표체.DNMT1、p16화cyclin D1재45례EB병독상관위암적양성례수분별위35례(77.8%)、10례(22.2%)화29례(64.4%),재40례EB병독음성위암적양성례수분별위20례(50.0%)、25례(62.5%)화12례(30.0%),3개분자재량조위암적표체솔차이균구유통계학의의(P＜0.05).p16여종류적침윤심도유관(P＜0.05).LMP2A여DNMT1、DNMT1여p16、p16여cyclin D1존재상관관계(P＜0.05).결론 엄주지구EB병독상관위암점위암구성비적6.7%(45/676),EB병독적잠복류형부분위Ⅰ형,부분개우Ⅰ형화Ⅱ형지간.LMP2A、DNMT1、p16화cyclin D1적상호작용재EB병독상관위암발생과정중기착중요적작용.
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.