Data from Methylation of <i>p16</i> CpG Island Associated with Malignant Progression of Oral Epithelial Dysplasia: A Prospective Cohort Study

Abstract

<div>Abstract<p><b>Purpose:</b> Inactivation of <i>p16</i> gene by CpG methylation is a frequent event in oral epithelial dysplasia. To investigate the predictive value of <i>p16</i> methylation on malignant potential in oral epithelial dysplasia, we carried out the prospective cohort study.</p><p><b>Experimental Design:</b> One hundred one patients with histologically confirmed mild or moderate oral epithelial dysplasia were included in the present cohort study. <i>p16</i> 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 <i>p16</i> methylation and progression of oral epithelial dysplasia was analyzed.</p><p><b>Results:</b> 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%. <i>p16</i> 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 <i>p16-</i>methylated oral epithelial dysplasia was significantly higher than that with the <i>p16-</i>unmethylated oral epithelial dysplasia (43.8% versus 17.4%; adjusted odds ratio, 3.7; <i>P</i> = 0.013), especially for patients at the baseline age of ≥60 years (adjusted odds ratio, 12.0; <i>P</i> = 0.003) and patients with moderate oral epithelial dysplasia (adjusted odds ratio, 15.6; <i>P</i> = 0.022). The overall sensitivity and specificity of prediction of malignant transformation of oral epithelial dysplasia by <i>p16</i> methylation were 63.6% and 67.9%, respectively.</p><p><b>Conclusion:</b> <i>p16</i> 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)</p></div>