RESUMO
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 .
Assuntos
Caderinas/genética , Metilação de DNA , DNA Viral/genética , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Regiões Promotoras Genéticas , Proteína do Retinoblastoma/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Antígenos CD , Caderinas/metabolismo , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Progressão da Doença , Epigênese Genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno , Testes de DNA para Papilomavírus Humano , Humanos , Gradação de Tumores , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Proteína do Retinoblastoma/metabolismo , Lesões Intraepiteliais Escamosas Cervicais/enzimologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/enzimologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Em pacientes com síndrome de Cushing, observa-se freqüência aumentada de infecções oportunistas que possuem uma elevada mortalidade e estão associadas à gravidade do hipercortisolismo. Criptococose pulmonar é uma destas infecções oportunistas e pode mimetizar uma neoplasia pulmonar, tornando o seu diagnóstico difícil. Apresentamos um caso de um paciente do sexo masculino, jovem, com síndrome de Cushing ACTH-dependente e grave hipercortisolismo. O paciente obteve a cura após cirurgia transfenoidal, mas desenvolveu quadro febril. Tomografia computadorizada de tórax mostrou um nódulo pulmonar que não se alterava em radiografias seriadas. A investigação para tuberculose, infecção fúngica e bacteriana foi inconclusiva, tornando a hipótese de neoplasia pulmonar mais provável. O paciente faleceu por sepse urinária. A necropsia, no entanto, demonstrou tratar-se de criptococose pseudotumoral. Pacientes com síndrome de Cushing e infiltrado pulmonar devem ser avaliados quanto à infecção fúngica, como Cryptococcus neoformans.
Assuntos
Adulto , Humanos , Masculino , Criptococose/complicações , Síndrome de Cushing/complicações , Pneumopatias Fúngicas/complicações , Criptococose/diagnóstico , Diagnóstico Diferencial , Evolução Fatal , Pneumopatias Fúngicas/diagnóstico , Neoplasias Pulmonares/diagnósticoRESUMO
Opportunistic infections in endogenous Cushing's syndrome are associated with severe cortisol excess and carry a high mortality. Pulmonary cryptococcosis is one of these opportunistic infections and can mimic a lung neoplasm, therefore making its diagnosis difficult. We report a case of a young male with ACTH-dependent Cushing's syndrome and severe hypercortisolism. The patient achieved cure after the transfenoidal surgery, but developed a febrile state. A chest computed tomography showed a pulmonary nodule that did not change in serial chest radiographs. Diagnosis of tuberculosis, fungal and bacterial infections were inconclusive, so the hypothesis of lung neoplasm became more probable. The necropsy, however, disclosed a pseudotumoral cryptococcosis. Opportunistic infections, like Cryptococcus neoformans, should be considered in patients with Cushing's syndrome and a pulmonary infiltrate.