Promoter hypermethylation of death-associated protein kinase and p16 genes in vulvar lichen sclerosus.

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.

Promoter hypermethylation patterns of death-associated protein kinase and p16 genes in vulvar lichen sclerosus.

OBJECTIVE: This article aimed to investigate the hypermethylation of promoter regions of tumor suppressor genes, such as death-associated protein kinase (DAPK) and p16, in vulvar lichen sclerosus (LS). MATERIALS AND METHODS: The promoter hypermethylation of DAPK and p16 was investigated from 15 vulvar biopsies of patients with LS who had had no previous treatment. DNA was treated with sodium bisulfate and underwent methylation-specific polymerase chain reaction of these genes. The amplified polymerase chain reaction products were analyzed by 10% polyacrylamide gel. RESULTS: The mean age of the patients was 57 years (most were postmenopausal). Methylation of the promoter region of DAPK was found in 2 (13%) of 15 patients analyzed, and p16 promoter region methylation was found in 7 patients (47%). The samples that showed DAPK methylation also showed p16 methylation. CONCLUSIONS: Methylation of DAPK and p16 represent alterations that might occur in cell cycle control in LS. The hypothesis is that patients who had methylated genes in this study, mainly the 2 cases in which there has been methylation in both studied genes, may be more susceptible to the development of differentiated vulvar intraepithelial neoplasia or vulvar cancer. Methylation may play a role in progress of vulvar carcinogenesis.

Epstein-Barr virus and human papillomavirus infection in vulvar lichen sclerosus.

OBJECTIVE: We investigated the presence of the Epstein-Barr virus (EBV) and human papillomavirus (HPV) in patients with vulvar lichen sclerosus (LS). MATERIALS AND METHODS: We investigated the presence of HPV and EBV from 34 vulvar biopsies of patients with LS who had had no previous treatment and from 17 normal vulvar brushings used as controls. We used polymerase chain reaction to amplify DNA sequences of these viruses. Human papillomavirus and EBV DNA detection was carried out using MY09/MY11 and TC67/TC69 consensus primers, respectively. The amplified polymerase chain reaction products were analyzed by 10% polyacrylamide gel. RESULTS: The mean age of the patients was 57 years old, with the majority postmenopausal. Human papillomavirus DNA was not found in the LS samples studied, but it was found in 23.2% (4/17) of the controls. However, EBV DNA was found in 26.5% (9/34) of the LS samples analyzed, and it was not found in the controls. CONCLUSIONS: Our results showed no relationship between HPV and LS. This result is in accordance with the literature. We have found 26.5% of EBV in our samples. This is a preliminary study, and the follow-up of these patients will elucidate whether EBV could play a role in cases of LS.

Neoplasia intraepitelial cervical / Cervical intraepithelial neoplasia

A neoplasia intraepitelial cervical (NIC) representa uma das manifestações subclínicas da infecção pelo papilomavírus humano (HPV). O diagnóstico e o tratamento dessas lesões são de grande importância, pelo fato de estarem intimamente relacionadas à gênese do câncer do colo uterino. Este artigo propõe-se a fazer uma revisão sobre os principais aspectos da epidemiologia, da história natural, do diagnóstico e do tratamento das NIC.

Cervical intraepithelial neoplasia (CIN) represent one of subclinical manifestations by Human Papillomavirus (HPV) infection. Diagnostic and treatment of CIN are extremely important because they are related with the carcinogenesis of cervical cancer. This article attempts to carry out a review on the main epidemiological data, natural history, diagnostic and treatment of CIN.

O papel do gene p16 e do gene Dapk no controle do ciclo celular e na via carcinogênese vulvar / The role of p16 and Dark genes in cell cycle control and in the pathways of vulvar carcinogenesis

O câncer vulvar é o quarto tipo de câncer mais comum nas mulheres e representa 4,8% dos cânceres do trato genital inferior. O carcinoma de células escamosas é responsável por 80 a 90% de todos os cânceres de vulva. O carcinoma escamoso vulvar e suas lesões pré-malignas parecem desenvolver-se por dois caminhos distintos, baseados em características etiológicas e histopatológicas, tendo assim uma etiologia heterogênea. Um dos caminhos está relacionado com a infecção pelo HPV, e o outro, com as desordens epiteliais, tais como líquen escleroso e hiperplasia epitelial. O HPV é um importante fator causal das neoplasias do trato genital inferior. Ele está presente em cerca de 90% dos cânceres do colo uterino e 30 a 40% dos cânceres de vulva. O tipo mais prevalente é o 16, seguido pelos tipos 18, 45, 31 e 33. O estudo das alterações genéticas e epigenéticas, por meio da análise de metilação e imunoexpressão gênica, tem demonstrado uma grande versatilidade para o monitoramento molecular de pacientes com câncer, o que impulsiona pesquisas de métodos diagnósticos e terapêuticos do câncer. Nesta atualização pretendeu-se demonstrar as funções dos genes p16 e DAPK e as recentes pesquisas sobre a expressão destes genes nas vias da carcinogênse vulvar.

Vulvar cancer is the fourth commonest kind of cancer in women and it represents 4.8% of cancers in the lower genital tract squamous cell carcinoma is responsible for 80-90% of all vulvar cancers. Squamous cell carcinoma and it's premalignant lesions seem to develop in two distinct pathways, based on etiological and histopathological characteristics, thus forming a heterogeneous etiology. Whereas one of the pathways is related to HPV infection, the other is related to epithelial disorders such as: lichen sclerousus and epithelial hyperplasia. HPV is an important contributing factor of neoplasia in the lower genital tract. It is found in 90% of cervical cancers and in 30-40 % of vulvar cancers. The most prevalent kind is 16, followed by 18, 45, 31, and 33. The study of genetic and epigenetic alterations by means of methylation and genic immunoexpression has demonstrated great versatility to the monitoring ofpatients with cancer, which boosts researches of diagnostic and therapeutic methods for cancer. This update intends to demonstrate the role of p16 and DAPK genes as well as the recent researches regarding the expression of these genes in the pathways of vulvar carcinogenesis.