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

Aidé, Susana PhD1; Lattario, Fernanda Ribeiro PhD2; Almeida, Gutemberg PhD1; do Val, Isabel Chulvis PhD1; Carvalho, Maria da Glória Costa PhD2

Journal of Lower Genital Tract Disease: April 2012 - Volume 16 - Issue 2 - p 133–139
doi: 10.1097/LGT.0b013e3182457fcc
Original Articles

Objective 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.

Materials and Methods 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.

Results 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).

Conclusions 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.

Methylation of death-associated protein kinase and p16 genes in lichen sclerosus may form part of a process of genetic and epigenetic alterations potentially relevant to malignant transformation.

1Vulvar Pathology Unit, Institute of Gynecology, and 2Gene Expression Control Laboratory, Carlos Chagas Filho Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Reprint requests to: Susana Aidé, PhD, Rua Doutor Tavares de Macedo, 121/602, Icaraí, Niterói, Rio de Janeiro, Brazil 24220-215. E-mail:

This study was carried out at both institutes.

This work was supported by the National Council for Scientific and Technological Development (CNPq or the National Research Council) and by the Ary Frauzino Foundation for Cancer Research and Prevention.

©2012The American Society for Colposcopy and Cervical Pathology