Molecular biologic and pathologic analysis of Epstein-Barr virus infection related salivary lymphoepithelial carcinoma

我们收集了180例经多种分子生物学方法证实为EB病毒感染的涎腺淋巴上皮癌（LEC）患者的组织标本，获得了EB病毒基因之一、被认为是癌基因的LMP 1基因的全序列。将其克隆到表达载体中，并将构建体转染到293 T细胞中。转染的细胞显示出NF κ B活性的显著升高和细胞生长的抑制，这在用具有不同LMP 1基因的载体转染的细胞中也被观察到，例如从鼻咽癌中分离的CAO和原型EBV B 95 -8。结果表明，LMP 1的表达影响LEC细胞的转录活性，但在本研究中发现的总体突变并不总是肿瘤发生的原因。对其中20例进行了LMP 1基因启动子区的分析，发现所有的病例都在与转录因子相关的区域发生了共同的突变。然而，不幸的是，很难从培养的细胞中建立细胞系。在其中一个原代培养中，我们成功地维持了细胞，这被证实是其唾液腺导管上皮和肌上皮的特征以及EBV感染。淋巴上皮囊肿作为一种背景疾病进行了研究，根据64例腮腺的临床病理分析。囊肿内的淋巴样间质可能是局部涎腺炎肉芽组织反应的结果，而不是EBV感染所致。我们的功能研究为EBV在涎腺LEC发病中的作用提供了新的认识，但其整个发病机制仍需进一步研究。

We have collected the total 180 cases of lymphoepithelial carcinoma (LEC) of salivary gland, which were confirmed as EBV-infected tumors by various molecular biological.A complete sequence for the LMP1 gene, one of the EBV gene and has been regarded as an oncogene, was obtained from patients' tissue samples. It was cloned into an expression vector and the constructs were transfected into 293T cells. The transfected cells showed significant elevation of NFkB activities and suppressed cell growth, which were also seen in cells transfected with vectors with different LMP1 genes such as CAO, which has been isolated from a nasopharyngeal carcinoma, and B95-8, a prototype EBV. The results indicated that the expression of LMP1 affects transcription activities in LEC cells but that the overall mutations found in the present study were not always reasons for the tumorigenesis. The promoter region of the LMP1 gene was also analyzed from 20 cases of them, and all of the cases shared common mutational events in regions that were expected to be associated with transcription factors.We tried primary cultures for salivary LECs for many times. Unfortunately, however, it was hard to establish cell lines from the cells in culture. In one of the primary cultures, we were successful in maintaining cells, which were confirmed to be their salivary duct epithelial and myoepithelial characteristics as well as EBV infected.As a background disease, lymphoepithelial cyst was studied based on clinicopathological analyses of sixty-four cases of the parotid gland. The lymphoid stroma of the cyst seemed to be resulted from granulation tissue reaction of focal sialadenitis but not induced by EBV infection.Our functional study shows a new insight for EBV roles in the pathogenesis of salivary LEC, although it is still necessary to carry out further investigations for the whole mechanisms of EBV oncogenesis.