Premium
High frequency of hypermethylation of p14, p15 and p16 in oral pre‐cancerous lesions associated with betel‐quid chewing in Sri Lanka
Author(s) -
Takeshima Maiko,
Saitoh Masato,
Kusano Kaoru,
Nagayasu Hiroki,
Kurashige Yoshihito,
Malsantha Muthumala,
Arakawa Toshiya,
Takuma Taishin,
Chiba Itsuo,
Kaku Tohru,
Shibata Toshiyuki,
Abiko Yoshihiro
Publication year - 2008
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2008.00644.x
Subject(s) - medicine , epithelial dysplasia , dysplasia , pathology , dna methylation , oral submucous fibrosis , cancer , immunohistochemistry , betel , leukoplakia , areca , biology , biochemistry , gene expression , structural engineering , nut , engineering , gene
Background: Oral squamous cell carcinoma and the most common oral pre‐malignancies appear to be related to the habit of betel‐quid chewing in Sri Lanka. Although hypermethylation of the tumour suppressor genes in oral cancer have been well documented, little information has been available concerning hypermethylation in oral pre‐cancerous lesions. In the present study, we investigated the hypermethylation of p14, p15 and p16 in pre‐cancerous lesions including epithelial dysplasia and submucous fibrosis. Methods: All samples were obtained from patients with a betel‐quid chewing habit in Sri Lanka. Sixty‐four patients were clinically diagnosed with leukoplakia, and histopathologically diagnosed with mild or severe dysplasia. Ten patients were diagnosed with submucous fibrosis without epithelial dysplasia. CpG island hypermethylation was assessed by a methylation‐specific PCR method. Immunohistochemical staining was performed using anti‐p53 antibodies. Results: A high frequency of hypermethylation of p14, p15 and p16 was detected in the pre‐cancerous lesions, although no hypermethylation was found in normal epithelium. The frequency of hypermethylation was higher than that of positive staining for p53 mutation except in the case of p16 in mild dysplasia. No significant correlation was observed between p53‐positive reactions and hypermethylation in any lesions. The hypermethylation was highly detectable even in p53‐negative lesions, suggesting that hypermethylation of p14, p15 and p16 occur regardless of whether the lesions have p53 mutations or not. Conclusions: The present study indicates that hypermethylation may be involved in the pathogenesis of oral pre‐cancerous lesions associated with betel‐quid chewing in Sri Lanka.