EB病毒感染及30 bp缺失潜伏膜蛋白1基因在鼻咽部癌不同组织学类型中的比较

目的 比较鼻咽部癌4种组织学类型中EB病毒的感染率以及野生型潜伏膜蛋白(LMP)1和缺失型LMPl EB病毒变异株单独或双重感染的检出频率,阐明缺失型LMPl基因在鼻咽癌变过程中的作用。方法 采用EBER原位杂交法检测117例鼻咽部癌,包括48例非角化性癌、25例角化性鳞状细胞癌、5例腺鳞癌、6例黏液表皮样癌和33例腺癌标本。采用巢式聚合酶链反应(PCR)法检测99例EBER阳性的癌组织和53个健康成人的外周血单个核细胞EB病毒LMPl基因。结果EBER原位杂交示,48例非角化性癌和25例角化性鳞状细胞癌的EB病毒感染率均为100％;而腺鳞癌和黏液表皮样癌的：EB病毒感染率为9／11,腺癌为51,5％(17／33)。阳性病例中大多数非角化性癌细胞呈EBER阳性,而在17例腺癌中仅见到少数EBER阳性肿瘤细胞。在非角化性癌中检测到单独缺失型LMPl：EB病毒变异株的百分率(85.4％,41／48)不但高于健康成人外周血单个核细胞(8．7％,4／46),而且高于角化性鳞状细胞癌(16．0％,4／25)。在角化性鳞状细胞癌中检出野生型LMPl和缺失型LMPl基因EB病毒的双重感染率(56．0％,14／25)高于非角化性癌的(12．5％,6／48)。在腺癌和健康成人单个核细胞中检出的大多数EB病毒为野生型LMPl和缺失型LMPl基因变异株同时并存。非角化性癌／角化性鳞状细胞癌、腺鳞癌／黏液表皮样癌和腺癌之间的：EB病毒感染率差异有显著性意义。非角化性癌和角化性鳞状细胞癌EB病毒的感染率相同,但非角化性癌中单独缺失型LMPl EB病毒变异株检出率远远大于角化性鳞状细胞癌,角化性鳞状细胞癌多数含有野生型LMPl和缺失型LMPl双重EB病毒变异株。结论由于分化导向不同而发生的鼻咽部癌不同组织学类型具有不同的EB病毒感染率。缺失型LMPl基因的EB病毒变异株可能在非角化性癌中呈选择性优势。

Comparison of the Epstein-Barr virus infection and 30 bp-deleted LMP1 gene among 4 histologic types of nasopharyngeal carcinoma

OBJECTIVE: To compare the Epstein-Barr virus (EBV) infection rates and the frequencies of wt-LMP1 and del-LMP1 EBV variants detected singly or dually among the four types of nasopharyngeal carcinoma (NPC) and to illustrate the possible role of del-LMP1 gene in nasopharyngeal carcinogenesis. METHODS: EBER in situ hybridization was performed in 117 NPCs, including 48 non-keratinizing carcinomas (NKCs), 25 keratinizing squamous cell carcinomas (KSCCs), 5 adenosquamous carcinomas (ASCs), 6 mucoepidermoid carcinomas (MECs) and 33 adenocarcinomas (ACs). Nested PCR for demonstration of EBV LMP1 gene was performed on the tissue samples collected from 99 EBER-positive carcinoma cases and the peripheral blood mononuclear cells (PBMCs) of 53 healthy adults (HAs). RESULTS: As indicated by EBER in-situ hybridization, the EBV infection rates in both of 48 NKCs and 25 KSCCs were 100%; and the infection rates of 11 ASCs/MECs and 33 ACs were 9/11 and 51.5% (17/33), respectively. Worthy to note was that most of the NKC cells were EBER-positive while only a small number of EBER-positive neoplastic cells could be found in 17 ACs. The percentage of del-LMP1 EBV variant detected singly in NKCs (85.4%, 41/48) was not only significantly higher than that in PBMCs of 46 HAs (8.7%, 4/46) but also significantly higher than those detected in KSCCs (16.0%, 4/25). The dual infection rate of wt-LMP1 and del-LMP1 variants detected in KSCCs (56.0%, 14/25) was significantly higher than that of NKCs (12.5%, 6/48). The majority of the EBV detected in AC tissues (12/17) and HAs' PBMCs (34/46, 73.7%) were of dual wt-LMP1 and del-LMP1 variants. CONCLUSIONS: The EBV infection rates are significantly different among 3 major histological categories, namely, NKC/KSCC, ASC/MEC and AC. Though NKCs and KSCCs are always consistently associated with EBV, the single del-LMP1 EBV variant detected in NKCs is predominant over that in KSCCs and most of the KSCCs contain dual wt-LMP1 and del-LMP1 EBV variants. The EBV of the del-LMP1 variant might play a crucial role in carcinogenesis of NKC.