The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: A promoter methylation and protein expression study in 100 cases
The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: A promoter methylation and protein expression study in 100 cases
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DOI：
10.1097/01.mp.0000085760.74313.dd
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发表时间：
2003-09-01
期刊：
影响因子：
7.5
通讯作者：
Fan, CY
中科院分区：
文献类型：
--
作者：
Ai, LB;Stephenson, KK;Fan, CY
p16 （CDKN2a/INK4a）基因是一个重要的肿瘤抑制基因，参与细胞周期调控的p16/周期蛋白依赖性激酶/视网膜母细胞瘤基因通路。p16蛋白被认为是该途径的负调节因子。该基因编码周期蛋白依赖性激酶4和6的抑制剂，其调节视网膜母细胞瘤基因的磷酸化和细胞周期的G1到S期转变。本研究通过甲基化特异性PCR和免疫组织化学染色分析了连续100例未经治疗的原发性头颈部鳞状细胞癌患者p16基因启动子超甲基化模式和p16蛋白表达。在头颈部鳞状细胞癌中，分别检测到27%和74%的p16启动子超甲基化和p16蛋白表达的明显缺失。chi(2)检验显示，酒精或烟草使用史与p16蛋白表达缺失显著相关（P = 0.005, P = 0.05）。05年,分别)。当患者随访数据与各种临床和分子参数相关时，肿瘤大小、淋巴结和临床分期是头颈部鳞状细胞癌患者无病生存（肿瘤复发）、病因特异性生存和总生存的最强预后预测因子。p16启动子超甲基化和p16蛋白表达的明显缺失似乎都不是一个独立的预后因素，尽管p16蛋白的缺失可能用于预测早期头颈部鳞状细胞癌患者的总体生存。
The p16 (CDKN2a/INK4a) gene is an important tumor-suppressor gene, involved in the p16/cyclin-dependent kinase/retinoblastoma gene pathway of cell cycle control. The p16 protein is considered to be a negative regulator of the pathway. The gene encodes an inhibitor of cyclin-dependent kinases 4 and 6, which regulate the phosphorylation of retinoblastoma gene and the G1 to S phase transition of the cell cycle. In the present study, p16 gene promoter hypermethylation patterns and p16 protein expression were analyzed in 100 consecutive untreated cases of primary head and neck squamous cell carcinoma by methylation-specific PCR and immunohistochemical staining. The p16 promoter hypermethylation and apparent loss of p16 protein expression were detected in 27% and 74% of head and neck squamous cell carcinoma, respectively. By chi(2) test, history of alcohol or tobacco use was significantly correlated with the loss of p16 protein expression (P = .005 and .05, respectively). When patient follow-up data were correlated with various clinical and molecular parameters, tumor size and nodal and clinical stage were the strongest prognostic predictors for disease-free survival (tumor recurrence) and for cause-specific and overall survival in patients with head and neck squamous cell carcinoma. Neither p16 promoter hypermethylation nor apparent loss of p16 protein expression appears to be an independent prognostic factor, although loss of p16 protein may be used to predict overall patient survival in early-stage head and neck squamous cell carcinoma.