Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions
Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions
复制标题
DOI：
10.1016/s0002-9440(10)65689-1
复制
发表时间：
1998-12-01
影响因子：
6
通讯作者：
Nakajima, T
中科院分区：
文献类型：
--
作者：
Sano, T;Oyama, T;Nakajima, T
p16蛋白（p16）是一种细胞周期蛋白依赖性激酶（CDK）抑制剂，其通过使视网膜母细胞瘤（Rb）蛋白磷酸化的CDK失活来减慢细胞周期。最近的生物学研究表明，p16的表达显着影响Rb的表达状态，和p16过表达已被证明在宫颈癌中，因为Rb的功能失活的人乳头瘤病毒（HPV）E7蛋白。为探讨p16过表达与HPV感染在宫颈癌发生中的关系，对139例宫颈和生殖器尖锐湿疣及肿瘤组织进行了p16蛋白免疫组化分析和HPV原位杂交及聚合酶链反应检测。在所有宫颈癌和伴有高危和中危HPV感染的癌前病变（即亚型16、18、31、33、52和58）中均观察到p16蛋白的显著过表达，即弥漫性和强免疫染色，尖锐湿疣和低度鳞状上皮内病变伴低危型HPV感染，如HPV-6/11例p16免疫组化染色呈局灶性和弱阳性。我们的研究结果清楚地表明，高，中危HPV病变的p16表达模式不同，其在低危HPV病变的表达，因此可能是由于不同的HPV的Rb蛋白的功能失活的差异。
The p16 protein (p16) is a cyclin-dependent kinase (CDK) inhibitor that decelerates the cell cycle by inactivating the CDKs that phosphorylate retinoblastoma (Rb) protein. Recent biological studies have revealed that p16 expression is markedly influenced by the status of Rb expression, and p16 overexpression has been demonstrated in cervical cancers because of functional inactivation of Rb by human papillomavirus (HPV) E7 protein. To clarify the relationship between p16 overexpression and HPV infection in cervical carcinogenesis, immunohistochemical analysis of p16 and detection of HPV by in situ hybridization and polymerase chain reaction were performed on 139 formalin-fixed and paraffin-embedded samples of cervical and genital condylomatous and neoplastic lesions. Marked overexpression of p16 protein, ie, diffuse and strong immunostaining, was observed in all cervical cancers and preneoplastic lesions with infection by high- and intermediate-risk HPVs, ie, subtypes 16, 18, 31, 33, 52, and 58, Condylomata acuminata and low-grade squamous intraepithelial lesions with infection by low-risk HPV such as HPV-6/11 showed focal and weak immunohistochemical staining for p16. Our results clearly showed that the mode of p16 expression in lesions with high- and intermediate-risk HPVs differed from its expression in lesions with low-risk HPVs and thus might be attributable to differences in functional inactivation of Rb protein by different HPVs.