RESUMEN
BACKGROUND: Human papillomavirus (HPV) inactivates the retinoblastoma 1 (RB1) gene by promoter methylation and reduces cellular E-cadherin expression by overexpression of DNA methyltransferase 1 (DNMT1). The Epstein-Barr virus (EBV) is an oncogenic virus that may be related to cervical carcinogenesis. In gastric cancer, it has been demonstrated that E-cadherin gene (CDH1) hypermethylation is associated with DNMT1 overexpression by EBV infection. Our aim was to analyze the gene promoter methylation frequency of RB1 and CDH1 and verify the association between that methylation frequency and HPV and EBV infection in cervical lesions. METHODS: Sixty-five samples were obtained from cervical specimens: 15 normal cervices, 17 low-grade squamous intraepithelial lesions (LSIL), 15 high-grade squamous intraepithelial lesions (HSIL), and 18 cervical cancers. HPV and EBV DNA testing was performed by PCR, and the methylation status was verified by MSP. RESULTS: HPV frequency was associated with cervical cancer cases (p = 0.005) but not EBV frequency (p = 0.732). Viral co-infection showed a statistically significant correlation with cancer (p = 0.027). No viral infection was detected in 33.3% (5/15) of controls. RB1 methylated status was associated with cancer (p = 0.009) and HPV infection (p = 0.042). CDH1 methylation was not associated with cancer (p = 0.181). Controls and LSIL samples did not show simultaneous methylation, while both genes were methylated in 27.8% (5/18) of cancer samples. In the presence of EBV, CDH1 methylation was present in 27.8% (5/18) of cancer samples. Only cancer cases presented RB1 promoter methylation in the presence of HPV and EBV (33.3%). CONCLUSIONS: The methylation status of both genes increased with disease progression. With EBV, RB1 methylation was a tumor-associated event because only the cancer group presented methylated RB1 with HPV infection. HPV infection was shown to be significantly correlated with cancer conditions. The global methylation frequency was higher when HPV was present, showing its epigenetic role in cervical carcinogenesis. Nevertheless, EBV seems to be a cofactor and needs to be further investigated. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159157579149317 .
Asunto(s)
Cadherinas/genética , Metilación de ADN , ADN Viral/genética , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/genética , Regiones Promotoras Genéticas , Proteína de Retinoblastoma/genética , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Antígenos CD , Cadherinas/metabolismo , Estudios de Casos y Controles , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Progresión de la Enfermedad , Epigénesis Genética , Infecciones por Virus de Epstein-Barr/virología , Femenino , Regulación Neoplásica de la Expresión Génica , Herpesvirus Humano 4/patogenicidad , Interacciones Huésped-Patógeno , Pruebas de ADN del Papillomavirus Humano , Humanos , Clasificación del Tumor , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Proteína de Retinoblastoma/metabolismo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/enzimología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/enzimología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
Methylation is a chemical modification in which a methyl group (CH3) is added to the cytosine in the promoter region of the gene. It involves a very frequent epigenetic event that is found in many human cancers. Currently, there is no consensus on whether methylation of the p16 gene could be used as a biomarker in cervical intraepithelial neoplasia. The authors studied the presence of methylation of the p16 gene and human papillomavirus (HPV) DNA, and a possible relationship between them in high-grade squamous intraepithelial lesions of the cervix. This case-control study analyzed 27 high-grade squamous intraepithelial lesion samples and 20 normal cytology samples. To detect p16 methylation, methylation-specific polymerase chain reaction was used, and for HPV DNA detection the polymerase chain reaction was performed by using MY09/MY11 and GP5+/GP6+ consensus primers. The presence of methylation of the promoter region of the p16INK4a gene was detected in 55.6% of the samples from the case group, whereas it was detected only in 20% of the samples from the control group (P=0.005). HPV DNA was found in 66.7% of the samples from the case group, whereas only 15% from the control group (P=0.0001). The relationship between the presence of methylation of the p16 gene and HPV DNA did not prove statistically significant in the case group (P=0.67) or the control group (P=0.51). In conclusion, the presence of methylation of the p16 gene constituted an occurrence that was early but independent of the presence of HPV DNA.
Asunto(s)
Carcinoma de Células Escamosas/patología , Metilación de ADN , ADN Viral/aislamiento & purificación , Genes p16 , Papillomaviridae/genética , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , ADN/metabolismo , Cartilla de ADN/genética , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Adulto JovenRESUMEN
Introdução: a sífilis congênita é uma das mais incabíveis causas de morbidez e mortalidade perinatal, o que revela uma assistência pré-natal ineficaz. A infecção intra-uterina pelo Treponema pallidum pode resultar em natimorto, morte neonatal, prematuro e/ou lesões sifilíticas que conduzem adesordens como surdez, prejuízo neurológico e deformidades ósseas. É infecção congênita que persiste em destaque, mesmo com a penicilina G benzatina reduzindo em quase 98% a transmissão materno-fetal quando a mãe é tratada adequadamente. Objetivo: neste trabalho apresenta-se o caso de uma gestação gemelar que teve como desfecho a morte intra-útero dos fetos, a retenção placentária e o choque hipovolêmico, culminando em histerectomia, ocorrido na maternidade do Hospital Escola Luiz Gioseffi Jannuzzi, em Valença, Rio de Janeiro. Relato do caso: relata-se a história de uma paciente de 33 anos, de classe socioeconômica baixa, multípara, admitida no serviço em trabalho de parto prematuro, com ambos os fetos mortos intra-útero. O parto foi transpélvico, com retenção placentária e choque hipovolêmico. Efetuado o pronto-atendimento, foi realizada a histerectomia e a estabilização do quadro. O VDRL, por razão da internação, revelou positividade, com início do tratamento. A paciente permaneceu internada oito dias. Conclusão: fica evidente que a sífilis é uma moléstia com graves conseqüências para as gestantes e seus conceptos, visto que 80% das mães infectadas sem tratamento, transmitem a doença para os fetos e um grande número destes morre antes de alcançar dois anos de idade.
Introduction: congenital syphilis is one of the most inappropriate morbidity causes and perinatal mortality, revealing ineffective prenatal care. Theintra-uterine infection for the Treponema pallidum can result in stillborn, neonatal death, premature and/or syphilitic lesions that lead to disorders as deafness, neurological damage and bone deformities. It is congenital infection that persists in prominence, although penicillin benzathine G prevents in almost 98% the maternal-fetal transmission, when the mother is treated correctly. Objective: this work presents the case of a twins` gestation that ended up with the death intra-uterus of fetuses, placental retention and shock due to loss of blood, culminating in hysterectomy, witch happened at theMaternity of Hospital School Luiz Gioseffi Jannuzzi, in Valença, Rio de Janeiro. Case report: the case of a 33 year-old patient who belonged to alow socioeconomic class, with several previous childbirths is related, she was admitted in the service in premature birth work, with both fetuses deadintra-uterus. The childbirth was transpelvic, with placental retention and shock due to loss of blood. With ready-attendance done, hysterectomy andthe stabilization of the case. VDRL, in cases of internment, revealed to be positive, in the beginning of the treatment. The patient stayed eight days in the hospital. Conclusion: it is evident that syphilis is a disease with serious consequences to pregnant women and their children, since, 80% of infectedmothers without treatment, they transmit the disease to the fetuses and several of them die before reaching two years old.