Promoter Hypermethylation of Death-Associated Protein Kinase and p16 Genes in Vulvar Lichen Sclerosus

Abstract

The purpose of this study was to discuss our investigation of the hypermethylation of promoter regions of tumor suppressor genes, such as death-associated protein kinase (DAPK) and p16, in vulvar lichen sclerosus (LS), in comparison with a control group. Promoter hypermethylation of DAPK and p16 was investigated using 24 vulvar biopsies of patients with LS who had received no previous treatment. The control group was composed of 15 patients with no vulvar disease. The DNA of subjects was treated with sodium bisulphate, and the genes under study were subjected to methylation-specific polymerase chain reaction. The resulting polymerase chain reaction products were amplified and analyzed using a 10% polyacrylamide gel. The mean age of the patients with LS was 57 years (the majority were postmenopausal). In the control group, the mean age of the patients was 50 years (p = .151). Methylation of the promoter region of DAPK was found in 4 (17%) of the 23 patients analyzed, and p16 promoter region methylation was found in 8 patients (35%). Two cases of methylation of the DAPK gene were also found to be methylated for the p16 gene. In the control group, no methylation was found in the patients analyzed for the DAPK gene and methylation was found in 3 (21%) of the 14 patients analyzed for the p16 gene (p = .190 and p = .316, respectively). Methylation of the DAPK and p16 genes, although not sufficient to dictate prognosis of the disease, should not be underestimated because it may form part of a process of genetic and epigenetic alterations that in the future could become relevant to malignant transformation.