Nasopharyngeal carcinoma
Nasopharyngeal carcinoma
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DOI：
10.1016/s0140-6736(97)07269-3
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发表时间：
1997-10-11
期刊：
影响因子：
168.9
通讯作者：
Weichselbaum, RR
中科院分区：
文献类型：
--
作者：
Vokes, EE;Liebowitz, DN;Weichselbaum, RR
EBV 感染始于口咽上皮。在原发感染过程的早期，EBV 还会感染 B 淋巴细胞，B 淋巴细胞是潜伏感染的主要部位，并且在感染传播到包括鼻咽在内的远端上皮表面方面也很重要。 EBV基因组是长度超过172千碱基对的双链DNA分子，编码100多个基因。已知大约有十个基因在病毒介导的细胞生长效应中发挥作用。对体外潜伏感染 B 淋巴细胞中 EBV 基因表达的研究发现，六种核蛋白 (EBNA) 和三种膜蛋白 (LMP) 可能介导 EBV 诱导的细胞增殖作用。 6 EBNA-1 几乎在所有病例中表达，LMP1 在约三分之二的 EBV 阳性 NPC 病例中表达。 EBNA-1 对于细胞分裂过程中病毒基因组的复制和维持非常重要。 LMP1 具有有效的生长改变作用，是啮齿动物成纤维细胞转化测定中的主要癌基因，并在体外对上皮细胞发挥生长改变作用。 7, 8 LMP1 还与肿瘤坏死因子 (TNF) 受体相关因子家族的成员结合，这些成员是 TNF 受体的信号传导中间体，表明 LMP1 可能作为 TNF 受体家族的信号传导同系物发挥作用。 9 NPC 和 EBV 之间的病因学联系首先基于血清学证据。经常出现针对病毒抗原的 IgG 和 IgA 抗体滴度升高。具体而言，与匹配的对照相比，鼻咽癌患者中针对 EBV 早期抗原复合物或病毒衣壳抗原的 IgA 抗体滴度较高。 10 项大型人群筛查试验已验证了 EBV 血清学在中国南方高危人群中用于鼻咽癌检测的用途。事实证明，前瞻性筛查对于检测临床前 NPC 非常有用，并且对于预测治疗后的复发也很有用。 10 随后，通过证明 EBV DNA 存在于 NPC 肿瘤细胞中，并且 NPC 活检样本中的 EBV DNA 是克隆的，源自单个 EBV 感染细胞，证实了 EBV 与 NPC 之间的关联。 11 这一观察结果表明，在致癌转化时 EBV 存在于细胞内，并表明该病毒在促成转化事件中发挥着作用。 EBV 也在癌前（浸润前）鼻咽病变中检测到，包括原位癌和不典型增生。 12 EBV 感染是克隆性的，表明病变代表局灶性细胞生长，并且 EBV 感染是 NPC 发展的早期事件。
EBV infections start in the oropharyngeal epithelium. Early in the course of primary infection, EBV also infects B lymphocytes that are the major site of latent infection and are also important in the dissemination of infection to distal epithelial surfaces including the nasopharynx. The EBV genome is a double-stranded DNA molecule of more than 172 kilobase pairs in length that encodes more than 100 genes. Approximately ten genes are known to play a part in virally mediated cell-growth effects. Studies on EBV gene expression in latently infected B lymphocytes in vitro have identified six nuclear proteins (EBNAs) and three membrane proteins (LMPs) which are likely to mediate EBV-induced effects on cell proliferation. 6 EBNA-1 is expressed in nearly all cases and LMP1 in about two thirds of cases of EBV-positive NPC. EBNA-1 is important in allowing replication and maintenance of the viral genome during cell division. LMP1 has potent growth-altering effects, is a dominant oncogene in rodent fibroblast transformation assays, and exerts growth-altering effects in epithelial cells in vitro. 7, 8 LMP1 also engages members of the tumour necrosis factor (TNF) receptor associated factor family, which are signalling intermediates for TNF receptors, suggesting that LMP1 may function as a signalling homologue of the TNF receptor family. 9 The aetiological link between NPC and EBV was first based on serological evidence. Elevated IgG and IgA antibody titres against viral antigens are frequently seen. Specifically, IgA antibodies directed against the EBV early antigen complex or viral capsis antigen are present in high titres in patients with NPC compared with matched controls. 10 Large population-based screening trials have validated the use of EBV serology for NPC detection in high-risk groups in Southern China. Prospective screening proved useful to detect preclinical NPC and has also been useful in the anticipation of recurrences after therapy. 10 The association between EBV and NPC was subsequently confirmed by showing that EBV DNA was present in the NPC tumour cells and that EBV DNA in NPC biopsy samples is clonal, arising from a single EBV infected cell. 11 This observation indicates that EBV is present within the cell at the time of carcinogenetic transformation and suggests a role for the virus in contributing to the transformation event. EBV has also been detected in premalignant (preinvasive) nasopharyngeal lesions, including carcinoma in situ and dysplasia. 12 EBV infection was clonal, indicating that the lesions represent a focal cellular growth and that EBV infection is an early event in the development of NPC.