Mahajan Aparna
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53705.
Hum Pathol. 2016 May;51:64-74. doi: 10.1016/j.humpath.2015.12.021. Epub 2016 Jan 19.
The p16 tumor suppressor gene (CDKN2A) is a member of the INK4 class of cell cycle inhibitors and is located on chromosome 9p21. The p16 protein binds to cyclin-dependent kinases 4 and 6 and maintains the retinoblastoma gene product in its hypophosphorylated state, which in turn binds to E2F transcription factor and prevents cell cycle progression. Expression of p16 protein is increased in aging cells. Immunohistochemistry for p16ink4a is most widely used as a surrogate maker for high-risk human papilloma virus infection in formalin-fixed, paraffin-embedded tissues. The most widely researched, accepted, and practiced use of p16 immunostain is in the lower anogenital tract. In addition, p16 immunostain is widely used for oropharyngeal squamous cell carcinoma. Its applications have also been extended to gynecologic tumors, which are unrelated to human papillomavirus. This article aims to review the literature on the diagnostic utility of p16 immunohistochemistry and highlight the practical issues in the application and interpretation of this stain.
p16肿瘤抑制基因（CDKN2A）是细胞周期抑制剂INK4家族的成员，位于9号染色体p21区域。p16蛋白与细胞周期蛋白依赖性激酶4和6结合，并使视网膜母细胞瘤基因产物维持在低磷酸化状态，进而与E2F转录因子结合，阻止细胞周期进程。衰老细胞中p16蛋白的表达会增加。在福尔马林固定、石蜡包埋的组织中，p16ink4a的免疫组织化学检测作为高危人乳头瘤病毒感染的替代标志物应用最为广泛。p16免疫染色研究最广泛、接受度最高且应用最多的领域是下生殖道。此外，p16免疫染色在口咽鳞状细胞癌中也有广泛应用。其应用还扩展到了与人乳头瘤病毒无关的妇科肿瘤。本文旨在综述p16免疫组织化学诊断效用的相关文献，并强调该染色应用和解读中的实际问题。
