应用组织微阵列技术研究EB病毒在鼻咽癌变中的作用  

Role of EBV in nasopharyngeal carcinogenesis:a tissue microarray study

作　　者：徐丽娜[1] 范松青[1] 李美蓉[1] 蒋谊[1] 梁青春[1] 李朵[1] 

机构地区：[1]中南大学湘雅二医院病理科,长沙410011

出　　处：《诊断病理学杂志》2008年第3期206-210,共5页Chinese Journal of Diagnostic Pathology

基　　金：湖南省自然科学基金资助(06JJ20013)

摘　　要：目的探讨EB病毒感染、突变型p53和bcl-2蛋白表达在鼻咽癌(NPC)发生、发展中的作用。方法组织微阵列技术结合原位杂交检测EBER-1和免疫组化检测p53和bcl-2蛋白在鼻咽癌变过程中不同病理形态组织的表达。结果①NPC组织中EBER-1阳性杂交信号、突变型p53蛋白和bcl-2蛋白阳性表达率显著高于增生鼻咽上皮、正常鼻咽上皮和异型增生鼻咽上皮(P<0.01);后者又显著高于前两者(P<0.01);异型增生鼻咽上皮和增生鼻咽上皮中p53蛋白阳性表达率也显著高于正常鼻咽上皮(P<0.05)。②临床Ⅲ、Ⅳ期NPC组织中p53和bcl-2蛋白阳性表达率显著高于临床Ⅰ、Ⅱ期(P=0.005,P=0.023)。NPC组织中EBER-1、p53和bcl-2蛋白表达间呈显著正相关(P<0.01)。③p53与EBER-1联合应用区分NPC与非癌鼻咽组织的灵敏度、特异度、阳性预测值、阴性预测值和符合率优于其他组合。结论鼻咽癌变的早期p53基因异常表达,随后继发EB病毒感染和bcl-2基因的激活,导致鼻咽上皮凋亡受阻、持续过度增殖,这在最终发展为NPC的过程中起着非常关键的作用。EBER-1和p53蛋白联合应用是区别NPC与非癌病变的较好分子标记。Objective To investigate whether the EBV infection, expression of mutant p53 protein and bcl-2 protein involve in the development and progression of nasopharyngeal carcinogenesis. Methods Tissue microarray technique combined with immunohistochemistry and in situ hybridization were used to detect the expression of EBER-1 （EBV-encoded small RNA, EBER- 1） hybridization signals, mutant p53 protein and bcl-2 protein in tissues of nasopharyngeal carcinogenesis process with differently pathological morphology. Results （ 1 ） EBER- 1 positive hybridization signals and positive expression of mutant p53 and bcl-2 proteins were significantly increased in NPC compared with histologically normal nasopharyngeal epithelium （NPE） and hyperplastic NPE （ P 〈 0.01）; EBER-1 and p53 protein in NPC were significantly higher than that in the dysplastic NPE （ P 〈 0.01 ） ; EBER-1 positive hybridization signals and positive expression of bcl-2 proteins were significantly increased in the dysplastic NPE compared with and hyperplastic NPE and histologically normal NPE （ P 〈 0.01 ） ; further statistic analysis confirmed that expression of p53 in the dysplastic NPE and hyperplastic NPE was higher than that in the normal NPE （ P 〈 0.05 ）. （2） Expression of p53 and bcl-2 proteins in clinical T3 and T4-staged NPC was evidently higher than that in T1 and T2-staged NPC （ P =0.005, P=0.023, respectively）; EBER-1 had significantly positive correlations with p53 and bcl-2 （P〈0.01）, also, p53 had evidently positive correlations with bcl-2 protein expression in NPC （ P 〈 0.01 ）. （3） Agreement rate, sensitivity, specificity, negative predictive values and positive predictive values, which were used to evaluate practical values of molecular markers to distinguish NPC from the non-cancerous NPE, revealed that combined application of molecular phenotype, EBER-1 and/or p53 protein over-expression was the best molecular approach. Conclusion Abnormal expression of p53 protein in the early stage of nas

关 键 词：鼻咽癌 组织微阵列 原位杂交 免疫组化 

分 类 号：R739.6[医药卫生—肿瘤]