Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Brazil.
Pathobiology. 2012;79(2):94-100. doi: 10.1159/000334926. Epub 2012 Jan 27.
The purpose of this study was to investigate the relationship between p16(CDKN2A) methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1). Finally, we tested whether HPV-16/18 or the dmt3b (C46359T) polymorphism is associated with p16(CDKN2A) methylation status.
To test the hypothesis, a case-control study with 72 (control, n = 24; ED, n = 48) tissue samples from subjects was performed. Methylation-specific PCR, RFLP, and immunohistochemical analyses were performed to evaluate p16(CDKN2A) methylation status, dmt3b (C46359T) genotyping, and protein levels, respectively.
The methylation of p16(CDKN2A) and HPV-16 was associated with ED gradation (p = 0.001 and 0.002, respectively). In addition, most HPV-16-positive samples (77.8%) exhibited p16(CDKN2A) methylation; however, changes in DNMT3B and DNMT1 protein levels were not observed in HPV-positive samples. Neither HPV-18 nor the dmt3b polymorphism was associated with p16(CDKN2A) methylation.
There is an association between the presence of HPV-16 in ED and the occurrence of p16(CDKN2A) methylation. Both variables are also associated with ED development, but further studies are necessary to clarify if they operate independently and if they have any impact on OD malignization.
本研究旨在探讨 p16(CDKN2A) 甲基化与上皮内瘤变（ED）之间的关系。我们还评估了与甲基化相关的蛋白质的表达（DNMT3B 和 DNMT1）。最后，我们检测了 HPV-16/18 或 dmt3b（C46359T）多态性是否与 p16(CDKN2A) 甲基化状态相关。
为了验证假设，我们进行了一项病例对照研究，共纳入 72 例（对照组，n=24；ED 组，n=48）组织样本。采用甲基化特异性 PCR、RFLP 和免疫组织化学分析分别评估 p16(CDKN2A) 甲基化状态、dmt3b（C46359T）基因分型和蛋白水平。
p16(CDKN2A) 甲基化和 HPV-16 与 ED 分级相关（p=0.001 和 0.002）。此外，大多数 HPV-16 阳性样本（77.8%）表现出 p16(CDKN2A) 甲基化；然而，在 HPV 阳性样本中未观察到 DNMT3B 和 DNMT1 蛋白水平的变化。HPV-18 或 dmt3b 多态性与 p16(CDKN2A) 甲基化无关。
ED 中 HPV-16 的存在与 p16(CDKN2A) 甲基化的发生有关。这两个变量也与 ED 的发生有关，但需要进一步的研究来阐明它们是否独立起作用，以及它们是否对 OD 恶变有影响。
