title: Differential hypermethylation of genes in vulvar cancer and lichen sclerosus coexisting or not with vulvar cancer.
abstract: Squamous cell carcinoma (SCC) of the vulva is a heterogeneous disease, associated or not with vulvar lichen sclerosus (LS). The precursor role of LS in vulvar cancer is unclear. We studied the epigenetic alterations of RASSF1A, RASSF2A, p16, TSP-1 and MGMT genes in vulvar SCCs, LS associated with SCC, isolated LS and normal vulvar skin. Gene hypermethylation and human papillomavirus presence were evaluated by methylation-specific PCR and PCR/reverse line blot, respectively. High-risk human papillomavirus types were present in 16.7% of the patients with vulvar SCC. There were increasing percentages of hypermethylation of genes from isolated LS to LS associated with vulvar SCC and vulvar SCC. The genes were hypermethylated more frequently in vulvar SCC associated with LS than in those not associated with LS, MGMT and RASSF2A being unmethylated in LS not associated with vulvar SCC. TSP-1 hypermethylation was related to recurrence in patients with vulvar cancer. Conclusions are as follows: (i) the epigenetic inactivation of genes is a common event in vulvar SCC and is also present in adjacent lesions, implying a possible precursor role for these alterations; (ii) MGMT and RASSF2A hypermethylation are present exclusively in vulvar SCC and LS associated with SCC, and absent from isolated LS; and (iii) TSP-1 hypermethylation is a bad prognosis factor in vulvar SCC.
authors: Biomedical Research Center, Navarra Health Service, Pamplona, Navarra, Spain. dguerres@cfnavarra.es
authors: David
authors: D
authors: Guerrero
authors: Rosa
authors: R
authors: Guarch
authors: Amaya
authors: A
authors: Ojer
authors: Juan Manuel
authors: JM
authors: Casas
authors: Carolina
authors: C
authors: Méndez-Meca
authors: Manel
authors: M
authors: Esteller
authors: Edurne
authors: E
authors: Barba-Ramos
authors: Federico
authors: F
authors: Garcia-Bragado
authors: Ana
authors: A
authors: Puras
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D018459:Lichen Sclerosus et Atrophicus / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014846:Vulvar Neoplasms / Q000235:genetics*