Mutational events of p53 gene in salivary gland tumors

为了解涎腺肿瘤中P53抑癌基因的突变情况，对117例涎腺肿瘤手术标本进行了DNA直接测序分析。标本包括淋巴上皮瘤35例、粘液表皮样癌30例、沃辛瘤33例、多形性腺瘤19例。同时，还对培养的腺样囊性癌细胞进行了检测。淋巴上皮瘤是一种具有淋巴间质的未分化癌，并与EB病毒感染有关。粘液表皮样癌和沃辛瘤的发病机制与广岛和长崎的原子弹电离辐射有关。然而，其他类型的唾液腺肿瘤的发病机制尚不清楚。这项调查是在目前积累的信息的背景下进行的。在本研究中，我们首先检查了…用聚合酶链式反应-荧光单链构象多态分析技术对p53基因第5-7外显子多个外显子进行直接测序。将检测结果与P53蛋白免疫组织化学染色结果进行比较。淋巴上皮瘤中最明显的P53基因突变发生在第5-7外显子，而P53蛋白免疫阳性较少。这些突变点在接受检查的病例中非常常见。相反，在多形性腺瘤中没有检测到明显的突变事件，即使在那些具有非典型细胞的腺瘤中也没有发现明显的突变事件，这些非典型细胞对p53基因产物显示出强烈的免疫反应。沃辛瘤和粘液表皮样癌常表现为外显子5和7的多个点突变，对氨基酸翻译的影响不大，这可能是该基因遗传多态的结果。然而，这些点突变在许多涎腺恶性肿瘤和良性肿瘤中都是相同的。这些结果表明，本研究中发现的p53基因外显子5和7的特定点突变是涎腺肿瘤发生的重要遗传背景。较少

In order to determine mutational events of the p53 tumor suppressor gene in salivary gland tumors, 117 cases of surgical materials of salivary tumors were analyzed by a direct sequencing of PCR products of DNA samples extracted from formalin-fixed paraffin-embedded tissue sections. The samples included 35 cases of lymphoepithelioma, 30 of mucoepidermoid carcinoma, 33 of Warthin tumor and 19 of pleomorphic adenoma. At the same time, cultured cells of adenoid cystic carcinoma were also examined.Lymphoepithelioma is an undifferentiated carcinoma with the lymphoid stroma and associated with the Epstein-Barr virus infection. The pathogeneses of mucoepidermoid carcinomas and Warthin tumors have been related to the exposure to ionizing radiation by atomic bomb in Hiroshima and Nagasaki. However, nothing is known about the pathogenesis for other types of salivary gland tumor. The investigation was performed in the background of the so far accumulated information.In this study we first examined … More exons 5-7 of p53 gene with PCR-fluoro-SSCP and then cases with abnormal SSCP profiles were subjected to direct sequencing. The results were compared with immunohistochemical staining patterns for p53 protein. Most conspicuous mutational events of p53 gens were found in exons 5-7 of lymphoepitheliomas, which instead showed scarce p53 protein immunopositivity. These mutational points were highly common among the cases examined. In contrast, no apparent mutational events were detected in pleomorphic adenomas, even in those with atypical cells that showed strong immunoreactions for p53 gene products. Warthin tumors and mucoepidermoid carcinomas often showed several point mutations in exons 5 and 7, which did not effect on amino acid translation so much, which seemed to be resulted from genetic polymorphism of the gene. However, these point mutations were shared by many cases of malignant and benign salivary gland tumors.These results suggest that the specific point mutations in exons 5 and 7 of the p53 gene found in the present study are important genetic background for salivary gland tumorigenesis. Less