鼻咽癌前期病变中的EB病毒感染(英文)  

Epstein-Barr Virus Infection in Precursor Lesions of Nasopharyngeal Carcinoma

作　　者：钟碧玲[1] 宗永生[1] 林素暇[2] 张敏 梁英杰[1] 

机构地区：[1]中山大学中山医学院病理学教研室 [2]华南肿瘤学国家重点实验室

出　　处：《癌症》2006年第2期136-142,共7页Chinese Journal of Cancer

基　　金：国家自然科学基金(No.39730200-II);广东省医学科研基金(No.A2004519)~~

摘　　要：背景与目的:鼻咽癌中的浸润性癌细胞均感染了EB病毒(Epstein-Barrvirus,EBV)。前期病变可见于早期鼻咽癌癌旁上皮。本研究旨在通过检测前期病变中的EB病毒,探讨EB病毒感染在鼻咽癌变过程中的作用,及其基因型在鼻咽癌变过程中发生的宿主内演变。方法:采用核酸原位杂交检测15例早期鼻咽癌活检组织中的EB病毒编码RNA(EBV-encodedRNA,EBER)。采用巢式PCR法检测前期病变和癌巢中的EB病毒类型和潜伏膜蛋白1(latentmembraneprotein1,LMP1)EB病毒株。具有代表性的LMP1基因羧基末端PCR产物采用四色荧光终止序列技术进行DNA序列分析。结果:所有15例早期鼻咽癌中的绝大多数浸润性癌细胞均呈EBER阳性。在15例前期病变中,14例可检测到EBER阳性的异常上皮细胞和/或浸润性淋巴细胞。单个A型EB病毒可在9例癌巢(11例适用)及9例前期病变(10例适用)的DNA样本中检测到。EB病毒LMP1基因羧基末端在15例癌巢DNA样本中均可检测到,其中14例是30bp缺失型LMP1EB病毒株,1例是野生型和30bp缺失型LMP1株的混合感染。在11例适合做EB病毒LMP1基因羧基末端扩增的前期病变的DNA样本中,5例呈野生型和30bp缺失型LMP1EB病毒株的混合感染,4例是单个缺失型LMP1EB病毒株感染,1例呈单个野生型LMP1EB病毒株感染,1例呈阴性反应。野生型LMP1基因羧基末端的DNA序列与B95-8细胞的DNA序列完全一致;30bp缺失型LMP1基因羧基末端的DNA序列却具有30bp缺失(密码子:346～355)和4个错义点突变(密码子:334、335、338和366)。结论:鼻咽上皮细胞的EB病毒感染是癌变过程中侵袭前的事件;而在鼻咽癌变过程中,EB病毒基因型会产生宿主内的演变。BACKGROUND ＆ OBJECTIVE： The infiltrating neoplastic cells within early-stage nasopharyngeal carcinoma （NPC） are consistently infected with Epstein-Barr virus （EBV）. The precursor lesions could often be found in paracancerous epithelium of early-stage NPC. This study was to investigate the role of EBV infection and the intrahost evolution of EBV genotype developed in nasopharyngeal carcinogenesis through detection of EBV harboring in precursor lesions. METHODS; EBV-encoded RNA （EBER） in 15 cases of early-stage NPC biopsy tissue was detected by nucleic acid in situ hybridization. EBV type and latent membrane protein 1 （LMP1） EBV strain in precursor lesions and carcinoma nests were detected by nested polymerase chain reaction （PCR）. DNA sequencing of the representative PCR products of carboxyl-terminus of LMP1 gene was analyzed by using four-colored fluorescence terminator sequencing technique. RERULTS： Most infiltrating carcinoma cells of all 15 cases of NPC showed EBER-positive. EBER-positive abnormal epithelial cells and/or infiltrating lymphocytes were found in 14 of 15 cases of precursor lesion. Single A-type EBV was detected in 9 of 11 available DNA samples of carcinoma nest and 9 of 10 available DNA samples of precursor lesion. The carboxyl-terminus of EBV LMP1 gene was detected in all 15 DNA samples of carcinoma nest, among which 14 were single 30-bp deleted LMP1 （deI-LMP1） EBV infection and 1 was coinfection of wild-type LMP1 （wt-LMP1） EBV strain and deI-LMP1 EBV strain. Among the 11 available DNA samples of precursor lesion suitable for carboxyl-terminus amplification, 5 were coinfection of wt-LMP1 and deI-LMP1 EBV, 4 were single deI-LMP1 EBV infection, 1 was single wt-LMP1 EBV infection, and 1 showed negative reaction. The DNA sequence of the carboxyl-terminus of wt- LMP1 gene was identical with that of B95-8 cells, while that of del-LMP1 gene had a 30-bp deletion （codon. 346-355） and 4 missense point mutations （codon： 334, 335, 338, and 366）. CONCLUSION. EBV in

关 键 词：EB病毒 前期病变 鼻咽肿瘤/病理学 

分 类 号：R739.63[医药卫生—肿瘤]