RESUMO
Current interest in the MUC1/EMA mucin relates to its role in malignancy, and its potential as a therapeutic target. MUC1/EMA expression has been observed in the majority of epithelioid mesotheliomas. However, little is known of the characteristics of MUC1/EMA in mesothelioma. Herein, we studied the cell surface and soluble expression of the MUC1/EMA glycoprotein, and determined the mRNA and genomic expression profiles in mesothelioma. We found that the anti-MUC1 antibody, E29, was the most diagnostically useful of seven antibody clones examined with a sensitivity of 84% (16 out of 19 cases) and no false positive results. MUC1 mRNA expression was significantly higher in mesothelioma samples than in benign mesothelial cells. No amplification of the MUC1 gene was observed by FISH. Seven of 9 mesothelioma samples expressed MUC1-secreted mRNA isoform in addition to the archetypal MUC1/transmembrane form. CA15.3 (soluble MUC1) levels were significantly higher in the serum of mesothelioma patients than in healthy controls but were not significantly different to levels in patients with benign asbestos-related disease. CA15-3 in effusions could differentiate malignant from benign effusions but were not specific for mesothelioma. Thus, as in other cancers, alterations in MUC1 biology occur in mesothelioma and these results suggest that specific MUC1 characteristics may be useful for mesothelioma diagnosis and should also be investigated as a potential therapeutic target.
Assuntos
Biomarcadores Tumorais/metabolismo , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Mucina-1/metabolismo , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Feminino , Regulação Neoplásica da Expressão Gênica , Glicosilação , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Mesotelioma/sangue , Mesotelioma/química , Pessoa de Meia-Idade , Mucina-1/análise , Mucina-1/sangue , Mucina-1/genética , Derrame Pleural Maligno/sangue , Derrame Pleural Maligno/química , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Sensibilidade e Especificidade , Regulação para CimaRESUMO
Conventionally reared and SPF laying hens were infected with egg drop syndrome (EDS) virus and killed at intervals during the first 13 days post inoculation (pi). Tissues were collected and studied using histo-pathological and immunoperoxidase techniques. EDS viral antigen and intranuclear inclusion bodies were detected in the surface epithelium of the nasal cavity of conventional hens 2 to 6 days pi. Low levels of viral antigen were detected in lymphoid tissue throughout the body 2 to 5 days pi and inflammatory lesions and viral antigen were observed in the infundibulum 3 to 5 days pi. Viral replication was first detected at a low level in the pouch shell gland (PSG) 8 days pi with extensive replication occurring in the PSG of hens killed subsequently. There was a good correlation between the presence of viral antigen and the presence of lesions. Viral antigen was never detected in the surface epithelium of the alimentary tract. These findings suggest that following EDS virus infection, viral replication occurs in the nasal epithelium, viraemia occurs and that the pouch shell gland is the main site of EDS virus replication in the laying hen. It is concluded that the reproductive tract is the most important source of virus for lateral spread in the laying hen.