Abstract
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. 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. 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. 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.
Highlights
Inactivation of p16 gene by CpG methylation is a frequent event in oral epithelial dysplasia
It was reported that about 8% of oral epithelial dysplasia progressed to oral squamous cell carcinoma [2, 3], the exact initial cause of malignant transformation of leukoplakia is not clear
Because it is impossible to identify the malignant potential of oral epithelial dysplasia lesions on histopathologic grounds alone, it attracts lot of attention to characterize molecular biomarkers for prediction of prognosis of oral epithelial dysplasia [20, 21]
Summary
Inactivation of p16 gene by CpG methylation is a frequent event in oral epithelial dysplasia. Aberrant inactivation of p16 gene by methylation is an early frequent event in multiple human cancers, including oral squamous cell carcinomas and its precancerous oral epithelial dysplasia lesions [9,10,11,12,13]. This article described our important finding that p16 methylation was correlated with malignant transformation of the oral dsyplasia significantly and could be a valuable biomarker for prediction of malignant potential of oral epithelial dysplasia with a high sensitivity (77%) and specificity (78%) for patients >60 years old. Based on the results of the present study, we suggest that detection of p16 methylation is a convenient assay and should be carried out as a regular test for patients with oral epithelial dysplasia Publication of these results on Clinical Cancer Research will be very helpful for promotion of its clinical application
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