Lambert Ana Paula Franco, Anschau Fernando, Schmitt Virgínia Minghelli
Laboratório de Biologia Molecular do Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Rua Prof. Cristiano Fischer 1118/201, Jardim do Salso, Porto Alegre/RS, CEP 91410-000, Brazil.
Exp Mol Pathol. 2006 Apr;80(2):192-6. doi: 10.1016/j.yexmp.2005.08.005. Epub 2005 Oct 28.
p16INK4a is a cyclin-dependent kinase (CDK) inhibitor which decelerates cell cycle by inactivating CDKs that phosphorylate pRb. Human Papillomavirus persistent infection plays an important role on cervical carcinogenesis, mainly by the action of two viral oncoproteins, E6 and E7, which interact with p53 and pRb, respectively. Increasing expression of E6 and E7 in dysplastic cervical cells might thus be reflected by increased expression of p16INK4a. Recent studies revealed that p16INK4a expression could be a marker for dysplastic and neoplastic cervical cells. The aim of this study was to analyze p16INK4a expression in cervical preneoplastic and neoplastic lesions and correlate with lesion grade. Expression of p16INK4a was analyzed by immunohistochemistry. A total of 6 low-grade squamous intraepithelial lesion (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 27 cancer samples were studied. In HPV-positive cervical samples (n=48), p16INK4a expression was observed in 1 of 3 LSIL, in 18 of 19 HSIL and in all 26 cancer cases. These results are in accordance with the hypothesis that functional inactivation of pRb by HPV-E7 protein induces p16INK4a expression in cervical lesions. In our study, a statistically significant association was observed between cervical lesion grade and p16INK4a expression (P<0.001).
p16INK4a是一种细胞周期蛋白依赖性激酶（CDK）抑制剂，它通过使磷酸化pRb的CDK失活来减缓细胞周期。人乳头瘤病毒持续感染在宫颈癌发生过程中起重要作用，主要通过两种病毒癌蛋白E6和E7的作用，它们分别与p53和pRb相互作用。因此，发育异常的宫颈细胞中E6和E7表达的增加可能反映为p16INK4a表达的增加。最近的研究表明，p16INK4a表达可能是发育异常和肿瘤性宫颈细胞的一个标志物。本研究的目的是分析p16INK4a在宫颈肿瘤前病变和肿瘤病变中的表达，并与病变分级相关联。通过免疫组织化学分析p16INK4a的表达。共研究了6例低级别鳞状上皮内病变（LSIL）、21例高级别鳞状上皮内病变（HSIL）和27例癌症样本。在HPV阳性的宫颈样本（n = 48）中，3例LSIL中有1例观察到p16INK4a表达，19例HSIL中有18例观察到p16INK4a表达，所有26例癌症病例均观察到p16INK4a表达。这些结果与HPV-E7蛋白使pRb功能失活诱导宫颈病变中p16INK4a表达的假说一致。在我们的研究中，观察到宫颈病变分级与p16INK4a表达之间存在统计学上的显著关联（P<0.001）。
