Methylation of p16 CpG Island Associated with Malignant Progression of Oral Epithelial Dysplasia: A Prospective Cohort Study

被引:77
作者
Cao, Jie [1 ]
Zhou, Jing [2 ]
Gao, Yan [1 ]
Gu, Liankun [2 ]
Meng, Huanxin [1 ]
Liu, Hongwei [1 ]
Deng, Dajun [2 ]
机构
[1] Peking Univ, Sch & Hosp Stomatol, Beijing 100081, Peoples R China
[2] Peking Univ, Key Lab Carcinogenesis & Translat Res, Beijing Canc Hosp Inst, Minist Educ,Dept Aetiol,Sch Oncol, Beijing 100081, Peoples R China
关键词
TUMOR-SUPPRESSOR GENE; PROMOTER METHYLATION; DNA METHYLATION; HUMAN CANCERS; NECK-CANCER; INACTIVATION; FREQUENCY; RISK; HEAD; TRANSFORMATION;
D O I
10.1158/1078-0432.CCR-09-0580
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Inactivation of p16 gene by CpG methylation is a frequent event in oral epithelial dysplasia. To investigate the predictive value of p16 methylation on malignant potential in oral epithelial dysplasia, we carried out the prospective cohort study. Experimental Design: One hundred one patients with histologically confirmed mild or moderate oral epithelial dysplasia were included in the present cohort study. p16 Methylation status of the oral epithelial dysplasia lesions from 93 cases was obtained by methylation-specific PCR. Progression of the oral epithelial dysplasia lesions was examined in 78 cases histologically during a 45.8 months follow-up period. The association between p16 methylation and progression of oral epithelial dysplasia was analyzed. Results: Of the 93 enrolled cases, 15 cases were lost during the follow-up because of changes of contact information, with a compliance of 83.9%. p16 Methylation was detectable in oral epithelial dysplasia lesions from 32 (41.0%) of 78 enrolled patients. Oral epithelial dysplasia-related squamous cell carcinomas were observed in 22 patients (28.2%) during the follow-up. Rate of progression to oral cancer in patients with the p16-methylated oral epithelial dysplasia was significantly higher than that with the p16-unmethylated oral epithelial dysplasia (43.8% versus 17.4%; adjusted odds ratio, 3.7; P = 0.013), especially for patients at the baseline age of 60 years (adjusted odds ratio, 12.0; P = 0.003) and patients with moderate oral epithelial dysplasia (adjusted odds ratio, 15.6; P = 0.022). The overall sensitivity and specificity of prediction of malignant transformation of oral epithelial dysplasia by p16 methylation were 63.6% and 67.9%, respectively. Conclusion: p16 Methylation was correlated with malignant transformation of oral epithelial dysplasia and is a potential biomarker for prediction of prognosis of mild or moderate oral epithelial dysplasia. (Clin Cancer Res 2009;15(16):5178-83)
引用
收藏
页码:5178 / 5183
页数:6
相关论文
共 26 条
[1]   Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort [J].
Belinsky, SA ;
Liechty, KC ;
Gentry, FD ;
Wolf, HJ ;
Rogers, J ;
Vu, K ;
Haney, J ;
Kenned, TC ;
Hirsch, FR ;
Miller, Y ;
Franklin, WA ;
Herman, JG ;
Baylin, SB ;
Bunn, PA ;
Byers, T .
CANCER RESEARCH, 2006, 66 (06) :3338-3344
[2]  
Bouquot J E, 1994, Quintessence Int, V25, P133
[3]   LEUKOPLAKIA, LICHEN-PLANUS, AND OTHER ORAL KERATOSES IN 23,616 WHITE AMERICANS OVER THE AGE OF 35 YEARS [J].
BOUQUOT, JE ;
GORLIN, RJ .
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY, 1986, 61 (04) :373-381
[4]   Management of oral epithelial dysplasia:: a review [J].
Brennan, Michael ;
Migliorati, Cesar A. ;
Lockhart, Peter B. ;
Wray, David ;
Al-Hashimi, Ibtisam ;
Axell, Tony ;
Bruce, Alison J. ;
Carpenter, William ;
Eisenberg, Ellen ;
Epstein, Joel B. ;
Holmstrup, Palle ;
Jontell, Mats ;
Nair, Raj ;
Sasser, Howell ;
Schifter, Mark ;
Silverman, Bud ;
Thongprasom, Kobkan ;
Thornhill, Martin ;
Warnakulasuriya, Saman ;
van der Waal, Isaac .
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY, 2007, 103 (03) :S19-S24
[5]   FREQUENCY OF HOMOZYGOUS DELETION AT P16/CDKN2 IN PRIMARY HUMAN TUMORS [J].
CAIRNS, P ;
POLASCIK, TJ ;
EBY, Y ;
TOKINO, K ;
CALIFANO, J ;
MERLO, A ;
MAO, L ;
HERATH, J ;
JENKINS, R ;
WESTRA, W ;
RUTTER, JL ;
BUCKLER, A ;
GABRIELSON, E ;
TOCKMAN, M ;
CHO, KR ;
HEDRICK, L ;
BOVA, GS ;
ISAACS, W ;
KOCH, W ;
SCHWAB, D ;
SIDRANSKY, D .
NATURE GENETICS, 1995, 11 (02) :210-212
[6]  
Danahey DG, 1999, ACTA OTO-LARYNGOL, V119, P285
[7]   Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: A population-based study [J].
Dong, Cai-Xuan ;
Deng, Da-Jun ;
Pan, Kai-Feng ;
Zhang, Lian ;
Zhang, Yang ;
Zhou, Jing ;
You, Wei-Cheng .
INTERNATIONAL JOURNAL OF CANCER, 2009, 124 (02) :434-439
[8]  
Gale N., 2005, Pathology and genetics of head and neck tumours, P177
[9]  
GONZALEZZULUETA M, 1995, CANCER RES, V55, P4531
[10]   p16 promoter methylation is a potential predictor of malignant transformation in oral epithelial dysplasia [J].
Hall, Gillian L. ;
Shaw, Richard J. ;
Field, E. Anne ;
Rogers, Simon N. ;
Sutton, David N. ;
Woolgar, Julia A. ;
Lowe, Derek ;
Liloglou, Triantafillos ;
Field, John K. ;
Risk, Janet M. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2008, 17 (08) :2174-2179