CLONAL PROLIFERATIONS OF CELLS INFECTED WITH EPSTEIN-BARR-VIRUS IN PREINVASIVE LESIONS RELATED TO NASOPHARYNGEAL CARCINOMA
CLONAL PROLIFERATIONS OF CELLS INFECTED WITH EPSTEIN-BARR-VIRUS IN PREINVASIVE LESIONS RELATED TO NASOPHARYNGEAL CARCINOMA
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DOI：
10.1056/nejm199509143331103
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发表时间：
1995-09-14
影响因子：
158.5
通讯作者：
RAABTRAUB, N
中科院分区：
文献类型：
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作者：
PATHMANATHAN, R;PRASAD, U;RAABTRAUB, N
背景。Epstein-Barr病毒（EBV）在鼻咽癌患者中一直被检测到。为了确定EBV感染是否为该恶性肿瘤发展的早期起始事件，我们筛选了大多数存档的鼻咽活检样本，以检查有无侵袭性病变，包括不典型增生和原位癌，在11个样本中发现了侵袭性病变，并对其进行了EBV检测。采用EBV编码rna （EBERs）的原位杂交和潜伏膜蛋白1 （LMP-1）的免疫组织化学染色检测EBV感染。较大的样本也使用Southern印迹法检测EBV基因组。用聚合酶链反应扩增互补DNA，检测特异性EBV rna的表达。在所有11例不典型增生或原位癌组织样本中均检测到EBV感染的证据，在所有8例检测样本中均检测到EBERs，在所有6例检测样本中均检测到LMP-1。7份检测EBV末端的样品中有6份含有EBV克隆DNA。在大多数样本中检测到潜伏的EBV基因产物EBV核抗原1、LMP-1、LMP-2A和BamHI-A片段的转录。未检出溶性病变特有的病毒蛋白。鼻咽部的侵袭前病变被eb病毒感染。EBV DNA是克隆性的，表明病变是由单个EBV感染细胞引起的局灶性细胞生长，表明EBV感染是鼻咽癌发展的早期，可能是初始事件。侵袭前病变含有潜伏性感染特征的EBV rna，但不含溶性感染特征的病毒蛋白。在所有肿瘤细胞中检测到ebv转化基因LMP-1，表明其表达对鼻咽癌相关的侵袭前上皮细胞增殖至关重要。
Background. The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ, Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.Methods. EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.Results. Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ, EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA. Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.Conclusions. Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.