Detection of Epstein-Barr virus gene products, p53 protein and bcl-2 protein in nasopharyngeal carcinoma.

鼻咽癌（NPC）是一种上皮性肿瘤，其发病率具有显著的地理和人群差异，与eb病毒（EBV）一致相关。在肿瘤内，EBV DNA就重复序列而言是同质和克隆的，这表明肿瘤也是克隆的。在本研究中，我们采用聚合酶链式反应（PCR）检测EBV- dna和原位杂交检测EBV编码小rna (EBERs)，以检测福尔马林固定石蜡包埋鼻咽癌标本中的EBV。3例角化鳞状细胞癌（SCC）、24例非角化癌（NKC）、13例未分化癌（UNPC）和2例腺癌（AC）均未检测到EBV-DNA。5例SCC中无EBERs， 32例NKC中30例，UNPC中16例，ac中无EBERs。在56例原发性鼻咽癌中，用BHLF寡核苷酸探针进行原位杂交，用LMP1、EBNA2、BZLF1蛋白、p53蛋白和bcl-2蛋白单克隆抗体进行免疫组化。17例（30%）检测到LMP1，而EBNA2未检测到。Bcl-2蛋白在50例（89%）中呈阳性，但其表达不依赖于LMP1的表达，LMP1在体外不诱导Bcl-2。18例（32%）细胞质中检测到BZLF1表达，而BHLF仅在6例（11%）中呈阳性。这一发现表明，尽管BZLF1的表达，但它破坏了病毒的潜伏期功能障碍。p53蛋白阳性31例（55%），BZLF1与p53蛋白表达有显著相关性（p<0.001）。提示BZLF1与p53相互失活的相互作用是鼻咽癌的致瘤因子之一

Nasopharyngeal carcinoma (NPC), an epithelial tumor which is characterized by marked geographic and population differences in incidence, is consistently associated with the Epstein-Barr virus (EBV). Within the tumor, the EBV DNA is homogeneous and clonal with regard to repeat sequences suggesting that the tumor is also clonal.In this work we examined to detect EBV in formalin-fixed paraffin-embedded NPC specimens by using both polymerase chain reaction (PCR) for EBV-DNA and in situ hybridization for EBV-encoded small RNAs (EBERs). EBV-DNA was detected in none of 3 keratinizing squamous cell carcinomas (SCC), 22 of 24 non-keratinizing carcinomas (NKC), all 13 undifferentiated carcinoma (UNPC) and none of 2 adenocarcinomas (AC). EBERs was detected in none of 5 SCC,30 of 32 NKC,16 of 17 UNPC and none of 2 AC.As an additional study in situ hybridization using BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed in 56 primary NPC.LMP1 was detected in 17 cases (30%) whereas EBNA2 was not detectable. 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 detectable in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This finding suggests BZLF1 which disrupts viral latency dysfunctions despite of 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 finding suggests the interaction between BZLF1 and p53 which inactivates each other is one of tumorigenic factor in NPC