Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study.
OBJECTIVE
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.


METHODS
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 > or = 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.


CONCLUSIONS
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.
Cao
Jie
J
Peking University School and Hospital of Stomatology, Beijing, China.
Zhou
Jing
J
Gao
Yan
Y
Gu
Liankun
L
Meng
Huanxin
H
Liu
Hongwei
H
Deng
Dajun
D
D000328:Adult; D000368:Aged; D000465:Algorithms; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018899:CpG Islands / Q000502:physiology; D019175:DNA Methylation / Q000502:physiology*; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D012680:Sensitivity and Specificity