Furukawa M, Nagayama I, Murono S, Takeshita H, Nishimura T, Yoshizaki T
Department of Otorhinolaryngology, School of Medicine, Kanazawa University.
Rinsho Byori. 1996 Sep;44(9):832-7.
In situ hybridization using EBERs and BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed on 56 primary nasopharyngeal carcinomas. EBERs was detected in 46 cases (82%), and LMP in 17 cases (30%), but EBNA2 was not detected. While 30 of 32 cases (94%) in differentiated non-keratinizing carcinoma (NKC) and 16 of 17 cases (94%) in undifferentiated carcinoma (UNPC) showed EBERs, neither 5 cases of squamous cell carcinoma (SCC) nor 2 cases of adenocarcinoma showed EBERs. This finding confirms latent infection of EBV, especially phenotypical latency II, in NKC and UNPC but not in SCC. Bcl-2 protein was positive in 50 cases (89%), but its expression did not depend on expression of LMP1, which did not demonstrate induction of bcl-2 by LMP1 as seen in vitro. Cytoplasmic BZLF1 expression was detected in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This suggests dysfunction of BZLF1, which disrupts viral latency despite its expression. p53 protein was positive in 31 cases (55%), and there was a distinct correlation between expression of BZLF1 and p53 protein (p < 0.001). This suggests that the interaction between BZLF1 protein and p53 protein, which inactivate each other, is one of the tumorigenic factors in NPC.
对56例原发性鼻咽癌进行了使用EBERs和BHLF寡核苷酸探针的原位杂交，以及使用抗LMP1、EBNA2、BZLF1蛋白、p53蛋白和bcl-2蛋白的单克隆抗体的免疫组织化学检测。46例（82%）检测到EBERs，17例（30%）检测到LMP，但未检测到EBNA2。在分化型非角化癌（NKC）的32例中有30例（94%），未分化癌（UNPC）的17例中有16例（94%）显示EBERs，而5例鳞状细胞癌（SCC）和2例腺癌均未显示EBERs。这一发现证实了EBV在NKC和UNPC中存在潜伏感染，尤其是II型表型潜伏感染，而在SCC中不存在。bcl-2蛋白在50例（89%）中呈阳性，但其表达不依赖于LMP1的表达，在体外未见LMP1诱导bcl-2表达的情况。18例（32%）检测到细胞质BZLF1表达，而BHLF仅在6例（11%）中呈阳性。这表明BZLF1功能异常，尽管其表达但仍破坏病毒潜伏状态。p53蛋白在31例（55%）中呈阳性，且BZLF1和p53蛋白的表达之间存在显著相关性（p<0.001）。这表明BZLF1蛋白和p53蛋白之间相互失活的相互作用是鼻咽癌的致瘤因素之一。
