Aberrant Protein Expression and Promoter Methylation of p16 Gene Are Correlated With Malignant Transformation of Salivary Pleomorphic Adenoma

Aberrant Protein Expression and Promoter Methylation of p16 Gene Are Correlated With Malignant Transformation of Salivary Pleomorphic Adenoma
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p16基因蛋白表达异常和启动子甲基化与唾液腺多形性腺瘤恶变相关。

DOI:
10.1043/2010-0181-oari.1
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发表时间:
2011-07-01
影响因子:
4.6
通讯作者:
Li, Jiang
Li, Jiang
中科院分区:
医学2区
文献类型:
--
作者:
Hu, Yu-Hua;Zhang, Chun-Ye;Li, Jiang

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上下文 p16基因启动子区甲基化和p16蛋白在涎腺癌(不包括多形性腺瘤)发生中的意义尚不清楚。Ca-ex-PA中p16基因启动子甲基化与p16蛋白表达和定位的关系有待进一步研究。 目的 目的:探讨p16蛋白表达和p16基因启动子区甲基化在多形性腺瘤癌变中的作用。 设计 采用免疫组化和甲基化特异性聚合酶链反应检测50例原发性涎腺Ca-ex-PA组织中p16蛋白表达和p16基因启动子甲基化。比较p16蛋白表达及p16基因启动子甲基化在良、恶性肿瘤中的差异。 结果 恶性肿瘤组织中p16蛋白的表达明显高于良性肿瘤组织,其表达主要集中在胞浆,而胞核的表达则明显低于良性肿瘤组织。恶性组织中p16基因启动子甲基化频率(36%)明显高于良性组织(16%)。p16基因启动子区甲基化与p16蛋白表达无相关性。 结论 p16蛋白在胞浆中的过度表达和在胞核中的低表达可能在多形性腺瘤向Ca-ex-PA的演变过程中起重要作用。p16基因启动子区甲基化可能与多形性腺瘤的恶变有关。
CONTEXT The significance of promoter methylation of the p16 gene and intracellular localization of p16 protein in the carcinogenesis of salivary carcinoma ex pleomorphic adenoma (Ca-ex-PA) is not clear. The correlation of the promoter methylation of the p16 gene and the expression and localization of p16 protein in Ca-ex-PA need to be further clarified. OBJECTIVE To investigate the p16 protein expression and promoter methylation of p16 gene in Ca-ex-PA and their roles in the malignant transformation of pleomorphic adenoma to Ca-ex-PA. DESIGN The p16 protein expression and promoter methylation of the p16 gene were determined in both benign and malignant components of 50 primary salivary Ca-ex-PA tissues by immunohistochemistry and methylation-specific polymerase chain reaction. Expression of p16 protein and promoter methylation of the p16 gene between the benign and the malignant components was compared statistically. RESULTS The tumor cells in the malignant components showed significantly higher p16 protein expression in the cytoplasm and lower expression in the nuclei than those in the benign components. Promoter methylation frequency of the p16 gene in the malignant components (36%) was significantly higher than that in the benign components (16%). There were no correlations between p16 protein expression and promoter methylation of the p16 gene in either benign or malignant components. CONCLUSIONS Overexpression of p16 protein in the cytoplasm and decreased expression of p16 protein in the nucleus may play important roles in the evolution of pleomorphic adenoma to Ca-ex-PA. Promoter methylation of the p16 gene may be correlated with the malignant transformation of pleomorphic adenoma.