EB病毒感染及30bp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

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

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LMP1EB病毒变异株单独或双重感染的检出频率 ,阐明缺失型LMP1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 4 8例非角化性癌、2 5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 5 3个健康成人的外周血单个核细胞EB病毒LMP1基因。结果 EBER原位杂交示 ,4 8例非角化性癌和 2 5例角化性鳞状细胞癌的EB病毒感染率均为10 0 % ;而腺鳞癌和黏液表皮样癌的EB病毒感染率为 9/ 11,腺癌为 5 1 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LMP1EB病毒变异株的百分率 (85 4 % ,4 1/ 4 8)不但高于健康成人外周血单个核细胞 (8 7% ,4 / 4 6 ) ,而且高于角化性鳞状细胞癌 (16 0 % ,4 / 2 5 )。在角化性鳞状细胞癌中检出野生型LMP1和缺失型LMP1基因EB病毒的双重感染率 (5 6 0 % ,14 / 2 5 )高于非角化性癌的(12 5 % ,6 / 4 8)。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LMP1和缺失型LMP1基因变异株同?

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 EBVvariant 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.