HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance.

BACKGROUND: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-ß mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). PATIENTS AND METHODS: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-ß mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. RESULTS: HOPX-ß mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. CONCLUSION: A moderate coupling of downregulation of HOPX-ß mRNA expression in DTC followed by high HOPX-ß promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.

Significant intrapulmonary Schistosoma egg antigens are not present in schistosomiasis-associated pulmonary hypertension.

Schistosomiasis-associated pulmonary arterial hypertension (PAH) is one of the most common causes of pulmonary hypertension worldwide. A potential contributing mechanism to the pathogenesis of this disease is a localized immune reaction to retained and persistent parasite-derived antigens. We sought to identify Schistosoma-derived egg antigens present in the lungs of individuals who died of the disease. We obtained 18 lung samples collected at autopsy from individuals who died of schistosomiasis-associated PAH in Brazil. A rabbit polyclonal antibody was created to known Schistosoma mansoni-soluble egg antigen (SEA). Histologic assessment and immunostaining of the human tissue was performed, along with immunostaining and immunoblotting of lung tissue from mice experimentally infected with S. mansoni. All 18 lung samples had evidence of pulmonary vascular remodeling with plexiform lesions and arterial medial thickening, but no visible eggs were seen. The anti-SEA antibody detected S. mansoni egg antigens in visible eggs in mouse lung and human intestine specimens, but did not identify a significant amount of egg antigen in the human lung specimens. In mouse granulomas containing degraded eggs, we observed colocalization of egg antigens and macrophage lysosomes. In conclusion, there is unlikely to be a significant amount of persistent parasite-derived antigens within the lungs of individuals who die of schistosomiasis-associated PAH. This suggests that retained and persistent parasite proteins are not contributing to a localized immune response in the pathogenesis of this disease.

Strongyloidiasis as an opportunistic infection in a HAM/TSP patient

Infection by human T-cell lymphotropic virus type I (HTLV-I) is associated with neurological diseases, malignancies, and other less commun pathologies. In addition, infection by HTLV-I has been implicated in some degree of immunological impairment. Some previous reports detected an association between HTLV-I infection and an increased rate of antibodies against S. stercoralis, as well as a higher frequency of S. stercoralis carrier state. Here, we report a case of a chronic, recurrent S. stercoralis parasitism in a patient infected by HTLV-I. The patient demonstrated evidence of immunosupression characterized by skin allergy to commun antigens, oral candidiasis and severe, recurrent diarrhea caused by S. stercoralis. The infection requires maintenance of supressive therapy to control diarrhea and its consequences. We postulate that S. stercoralis may act as an opportunistic agent in patients infected by HTLV-I.

Tiroidite de Hashimoto: correlaçäo clínico-citológica / Hashimoto thyroiditis: clinic-cytological correlation

Foram estudados 85 pacientes portadores de bócio com diagnóstico clínico-citológico de tiroídite de Hashimoto. Oitenta e um pacientes (95 por cento) eram do sexo feminino e 4 (15 por cento) do sexo masculino, com idade média de 40,4 + 14,6 anos, variando entre 11 a 88 anos. Cinco indivíduos (5,9 por cento) tinham idade menor que 20 anos e 4 deles (9,4 por cento) idade superior a 60 anos. Todos foram submetidos a citologia aspirativa de agulha fina de tiroide (CAAF) e os dados clínicos e exames complementares foram correlacionados com os achados citológicos. Notou-se diversidade de apresentaçao clínica e laboratorial da tiroidite de Hashimoto: o bócio era do tipo nodular em 55 por cento dos casos (cintilograficamente "frios" em 62 por cento e "mornos" em 38 por cento) e considerado difuso em 45 por cento. A funçao tiroidiana era norínal em 59 por cento, diminuída em 26 por cento e aumentada em 15 por cento. A pesquisa de anticorpos anti-microssomal (n=50) foi considerada positiva (1:400) em 72 por cento e negativa em 18 por cento dos pacienteç. O estudo citopatológico mostrou que pelo menos 3 critérios estavam sempre presentes na tiroidite de Hashimoto: infiltraçao linfo-histio-plasmocitária, esboço de folículos linfóides e colóide. Constatou-se que a CAAF é de grande auxílio no diagnóstico de tiroidite de Hashimoto, podendo, isoladamente, confirmar este diagnóstico em 83,5 por cento dos pacientes estudados. Nos casos em que os critérios citológicos sao apenas sugestivos, é importante a correlaçao com os dados clínicos, laboratoriais e cintilográficos para melhor definir o diagnóstico.