As mucinas e o NCAM (CD56) na colangiocarcinogênese intra-hepática / Mucins and NCAM (CD56) in intrahepatic cholangiocarcinogenesis

Introduction: Cholangiocarcinoma is the second most common malignant neoplasm of the hepatobiliary system. During cholangiocarcinogenesis phenotypic changes occur in the ductal epithelium, including the expression of mucins (MUC). However, the evaluating studies of the expression of mucins in the different stages of cholangiocarcinogenesis are scarce. CD56 has also contributed in differentiating benign ductal proliferation and cholangiocarcinoma; however, its expression has not been evaluated in dysplastic epithelium of the bile duct yet. Objective: To assess immunohistochemical profile of (MUC) 1, 2, 5, 6, and CD56 in cholangiocarcinoma, pre-neoplastic and reactive lesions in the epithelium of intrahepatic bile ducts. Material and methods: Immunohistochemical expression of MUC 1, 2, 5, 6, and CD56 were studied for 11 cases of cholangiocarcinoma and 83 intrahepatic bile ducts (67 reactive and 16 dysplastic). Variables were considered significant when p < 0.05. Results: The expression of MUC1 occurred in about 90% of the cholangiocarcinomas, contrasting with the low frequency of positive cases in reactive and dysplastic bile ducts (p < 0.001). However, there was no statistically significant difference in the expression of MUC5, MUC6 and CD56 between the reactive or dysplastic lesions and cholangiocarcinoma. The anti-MUC2 antibody was negative in all cases. Conclusions: MUC1 contributed for the differential diagnosis between cholangiocarcinoma and pre-neoplastic and reactive/regenerative lesions of intrahepatic bile ducts, and it should compose the antibodies panel aiming at improvement of these differential diagnoses. In contrast, MUC2, MUC5, MUC6 and CD56 were not promising in differentiating all the phases of cholangiocarcinogenesis...

Introdução: O colangiocarcinoma é a segunda neoplasia maligna mais comum do sistema hepatobiliar. Durante a colangiocarcinogênese podem ocorrer alterações fenotípicas do epitélio ductal, incluindo a expressão de mucinas. Entretanto, os estudos que avaliam a expressão das mucinas nas diferentes etapas da colangiocarcinogênese são escassos. O CD56, apesar de contribuir na diferenciação entre as proliferações ductais benignas e o colangiocarcinoma, ainda não teve a sua expressão avaliada no epitélio displásico dos ductos biliares. Objetivos: Analisar o perfil das mucinas (MUC) 1, 2, 5, 6 e do CD56 no colangiocarcinoma, nas lesões pré-neoplásicas e reacionais de ductos biliares intra-hepáticos. Material e métodos: A expressão imuno-histoquímica da MUC 1, 2, 5, 6 e do CD56 foram avaliadas em 11 colangiocarcinomas e 83 ductos biliares intra-hepáticos (67 reativos e 16 displásicos). As variáveis foram consideradas como significativas quando p < 0,05. Resultados: A expressão da MUC1 ocorreu em cerca de 90% dos colangiocarcinomas, contrastando com a baixa frequência de casos positivos nos ductos biliares reativos ou displásicos (p < 0,001). Não houve diferença estatisticamente significativa na expressão de MUC5, MUC6 e CD56 entre as lesões reativas, displásicas e o colangiocarcinoma. O anticorpo anti-MUC2 foi negativo em todos os casos. Conclusão: A MUC1 contribuiu no diagnóstico diferencial entre o colangiocarcinoma e as lesões pré-neoplásicas e reacionais/regenerativas dos ductos biliares intra-hepáticos, e deve compor o painel de anticorpos a ser empregado visando o aprimorando destes diagnósticos diferenciais. Contrariamente, a MUC2, MUC5, MUC6 e o CD56 não se mostraram promissoras na diferen...

Expression of ABC transporters, p53, Bax, Bcl-2 in an archival sample of non-small cell lung cancer bearing a deletion in the EGFR gene.

EGFR mutations have been correlated to responsiveness to treatment with tyrosine kinase inhibitors. These drugs are themselves substrates for ABC transporters. In the present work we describe the immunohistochemical profile of an archival sample from a male Brazilian patient with no Asian ancestry and never smoker, diagnosed with non-small cell lung cancer. This tumor was found to contain an in-frame hemi- or homozygous deletion, E746-A750 in exon 19 of the EGFR gene. Immunohistochemistry revealed a relatively weak staining for the ABC transporter subfamily ABCC1 and strongly for ABCB1. The cytoplasm stained positively for Bax and the nucleus stained for p53, but was negative for Bcl-2. Antibody against acetylated lysine revealed staining in both, cytoplasm and nucleus of tumor cells in contrast to normal cells which were essentially negative. The overall immunohistochemistry pattern obtained for this sample indicates that the del E746-A750 mutation may have down-regulated the expression of ABCC1. The results also suggest that the NSCLC analyzed displayed a transcriptionally active chromatin as judged by the results obtained with the anti-acetylated lysine antibody.