Epstein-Barr virus infection is an early event in gastric carcinogenesis and is independent of bcl-2 expression and p53 accumulation
Epstein-Barr virus infection is an early event in gastric carcinogenesis and is independent of bcl-2 expression and p53 accumulation
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DOI：
10.1016/s0046-8177(96)90133-1
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发表时间：
1996-01-01
期刊：
影响因子：
3.3
通讯作者：
Schneider, BG
中科院分区：
文献类型：
--
作者：
Gulley, ML;Pulitzer, DR;Schneider, BG
采用针对eb病毒编码RNA 1 （EBER1）转录物的敏感原位杂交技术，对95例胃腺癌患者进行了eb病毒（EBV）检测。95例中有11例（12%）检测到EBER1。当存在时，病毒局限于恶性上皮细胞和发育不良的胃上皮，但在正常的胃上皮或肠化生中未见。通过对EBV末端重复片段的Southern blot分析，这3例病例的EBV DNA均为单克隆。这些发现表明病毒在恶性转化之前就存在了。EBV的存在与肿瘤浸润性T淋巴细胞数量增加密切相关；然而，EBV与延长生存期无关。p53和bcl-2在ebv相关肿瘤中均未被一致检测到。具体来说，免疫组化分析显示，6例Ii型EBV阳性癌中p53蛋白积累，这与EBV阴性标本中p53蛋白积累的发生率相似，表明EBV感染不能替代肿瘤发生过程中的p53突变。bcl-2癌蛋白在三分之一的癌标本中表达，但bcl-2的表达与EBV的存在或EBV潜伏膜蛋白1的表达无关。总之，EBV感染在很大一部分胃癌中似乎先于恶性转化，但bcl-2的表达和p53的积累似乎都与病毒的存在不一致。
Ninety-five cases of adenocarcinoma of the stomach were evaluated for the presence of Epstein-Barr virus (EBV) using a sensitive in situ hybridization assay targeting Epstein-Barr virus-encoded RNA 1 (EBER1) transcripts. EBER1 was detected in 11 of 95 (12%) of cases. When present, the virus was localized to malignant epithelial cells and to dysplastic gastric epithelium, but was not seen in normal-appearing gastric epithelium or intestinal metaplasia. The EBV DNA was monoclonal in all three cases tested by Southern blot analysis of the EBV terminal repeat fragment. These findings suggest that the virus was present before malignant transformation. The presence of EBV was strongly associated with increased numbers of tumorinfiltrating T lymphocytes; however, EBV was not associated with prolonged survival. Neither p53 nor bcl-2 were consistently detected in the EBV-associated tumors. Specifically, 6 of Ii EBV-positive carcinomas had accumulation of p53 protein by immunohistochemical analysis, which was similar to the prevalence of p53 accumulation in EBV-negative specimens and suggests that EBV infection does not substitute for p53 mutation during tumorigenesis. The bcl-2 oncoprotein was expressed in a third of the carcinoma specimens tested, but bcl-2 expression did not correlate with the presence of EBV or with expression of EBV latent membrane protein 1. In conclusion, EBV infection appears to precede malignant transformation in a significant fraction of gastric carcinomas, but neither bcl-2 expression nor p53 accumulation appear to be consistently associated with the presence of the virus.