Lim Kue Peng, Hamid Sharifah, Lau Shin-Hin, Teo Soo-Hwang, Cheong Sok Ching
Cancer Research Initiatives Foundation, 2nd Floor Outpatient Centre, Subang Jaya Medical Centre, 47500 Subang Jaya, Selangor, Malaysia.
Oncol Rep. 2007 Jun;17(6):1321-6.
Inactivation of the retinoblastoma (pRB) pathway is a common event in oral squamous cell carcinoma particularly through the aberrant expression of the components within this pathway. This study examines the alterations of molecules within the pRB pathway by looking at the presence of homozygous deletions in p16(INK4A) and the expression patterns of pRB, cyclin D1 and CDK4, as well as the presence of human papillomavirus (HPV) in our samples. In our study, 5/20 samples demonstrated deletions of p16(INK4A) exon 1alpha. pRB overexpression was found in 20/20 samples, the expression was mainly observed in all layers of the epithelia, particularly in the basal layer where cells are actively dividing and aberrant pRB expression was found in 12/20 samples. Cyclin D1 and CDK4 overexpression was detected in 6/20 and 2/20 samples respectively in comparison to hyperplasias where both proteins were either not expressed or expressed at minimal levels (<10%). Strikingly, HPV was found to be present in all of our samples, suggesting that HPV plays a significant role in driving oral carcinogenesis. Notably, 17/20 of our samples showed more than one alteration in the pRB pathway, however, we did not find any significant relationship between the presence of HPV, homozygous deletion of p16(INK4A) and overexpression of pRB, cyclin D1 and CDK4. Collectively, this data demonstrates that alterations in the pRB pathway are a common event and involve the aberration of more than one molecule within the pathway. Furthermore, the involvement of HPV in all our samples suggests that HPV infection may play an important role in oral carcinogenesis.
视网膜母细胞瘤（pRB）通路的失活在口腔鳞状细胞癌中是常见事件，尤其是通过该通路内各组分的异常表达。本研究通过观察p16（INK4A）纯合缺失的存在情况、pRB、细胞周期蛋白D1和细胞周期蛋白依赖性激酶4（CDK4）的表达模式以及我们样本中人类乳头瘤病毒（HPV）的存在情况，来检测pRB通路内分子的改变。在我们的研究中，20个样本中有5个显示p16（INK4A）外显子1α缺失。20个样本中均发现pRB过表达，该表达主要见于上皮各层，尤其是在细胞活跃分裂的基底层，20个样本中有12个发现pRB异常表达。与增生组织相比，细胞周期蛋白D1和CDK4过表达分别在20个样本中的6个和2个中检测到，在增生组织中这两种蛋白要么不表达，要么表达水平极低（<10%）。令人惊讶的是，我们所有样本中均发现HPV存在，这表明HPV在口腔癌发生过程中起重要作用。值得注意的是，我们20个样本中有17个在pRB通路中显示不止一种改变，然而，我们未发现HPV的存在、p16（INK4A）纯合缺失与pRB、细胞周期蛋白D1和CDK4过表达之间存在任何显著关联。总体而言，这些数据表明pRB通路的改变是常见事件，且涉及该通路内不止一种分子的异常。此外，我们所有样本中均有HPV参与，这表明HPV感染可能在口腔癌发生中起重要作用。
