Hypermethylation of the p16 gene promoter in pterygia and itsassociation with the expression of DNA methyltransferase 3b

[摘要] Purpose: A pterygium has long been considered as a degenerativecondition. After p53 protein was found to be abnormally expressed in theepithelium, researchers suggested that a pterygium may be a tumor, butadditional evidence is required to support this hypothesis. Aberrantmethylation of the p16 gene (CDKN2A) promoter and resultant genesilencing play important roles in the pathogenesis of many types ofhuman cancers. The purpose of this study was to investigatehypermethylation of the p16 promoter in pterygia and therelationship between this hypermethylation and the expression of p16 andDNA methyltransferase 3b (DNMT3b) proteins.Methods: We studied the methylation status of p16 and theexpression of p16 and DNMT3b proteins by performing methylation-specificpolymerase chain reaction and immunohistochemistry, respectively, inspecimens of 129 pterygia and 16 normal conjunctiva. The results werestatistically analyzed.Results: Hypermethylation of the p16 gene promoter was detected in21 (16.3%) of 129 pterygial specimens. Among them, 46 (35.7%) werepositive for p16 protein expression, and 83 (64.3%) were negative.Staining for p16 was limited to the nuclei of the epithelial layer. Weobserved a significant reverse correlation between hypermethylation ofthe p16 promoter and the expression of p16 protein (p=0.006).Thirty-eight (29.5%) pterygial specimens were positive for DNMT3bprotein expression, and 91 (70.5%) were negative. DNMT3b staining waslimited to the nuclei of the epithelial layer. A significant correlationwas found between hypermethylation of the p16 promoter and theexpression of DNMT3b protein (p<0.001).Conclusions: The p16 gene promoter was hypermethylated inpterygia, and this hypermethylation was strongly linked to expression ofthe positive expression of DNMT3b protein and to the suppression of p16protein. These data provided molecular evidence that methylation occursin pterygia and that it may play a role in the their development.

[学科分类] 生物化学/生物物理