Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.
Trabalho baseado na dissertação apresentada ao Programa de Pós-Graduação em Patologia da Faculdade de Medicina de Botucatu da UNESP para obtenção do título de Mestre em Patologia. Trabalho apresentado na sessão de pôsteres do Congresso Brasileiro de Patologia, Salvador/BA, 2001. J Bras Patol Med Lab • v. 40 • n. 4 • p. 265-71 • agosto 2004 y unitermos key words resumo Introdução: A hiperexpressão de human epidermal growth factor receptor (HER-2/neu) e a amplificação do seu gene são indicadores de formas mais agressivas do câncer de mama. A Food and Drug Administration (FDA) aprovou o teste denominado HercepTest ® com a finalidade de selecionar pacientes com indicação para o uso de um anticorpo humanizado anti-HER-2/neu (trastuzumab), com efeito terapêutico comprovado. Objetivos: O presente trabalho tem como objetivo comparar os resultados obtidos pelos métodos imuno-histoquímicos LSAB ® + com a utilização de anticorpo A0485 e HercepTest ® . Material e métodos: Foram utilizados 50 casos de carcinoma de mama nos quais a pesquisa da hiperexpressão de HER-2 pelo método LSAB ® + já havia sido realizada. Foi repetida a pesquisa da hiperexpessão de HER-2/neu nos mesmos casos, utilizando-se o método do HercepTest ® . Resultados: 34 casos foram considerados negativos pelos dois métodos, com escore 0 pelo método HercepTest ® . Destes, 12 obtiveram escore 1+ e 22 obtiveram escore 0 pelo método LSAB ® +. Em oito casos, o escore foi 2+ pelos dois métodos. Escore 3+ foi encontrado também em oito casos pelos dois métodos. Discussão: O método mais prático utilizado em laboratório de rotina diagnóstica para investigar a hiperexpressão de HER-2/neu é o estudo imuno-histoquímico. Em função de muitas variáveis, como tempo de fixação, tipo de fixador, duração da fixação, método de recuperação antigênica e tipo de anticorpo utilizado, pode haver divergência de resultados. Conclusão: O presente estudo concluiu que o método HercepTest ® demonstrou resultados equivalentes aos resultados obtidos pelo método LSAB ® + em carcinoma de mama. Carcinoma Mama C-erbB-2 HER-2/neuHiperexpressão Imuno-histoquímica abstract Introduction: The overexpression of human epidermal growth factor receptor (HER-2/neu) protein and the amplification of its gene are indicators of more aggressive behavior in breast cancer. The Food and Drug Administration (FDA) has approved HercepTest ® with the goal of selecting patients to be elegible for treatment with the humanized murine monoclonal antibody anti-HER-2/neu (trastuzumab). Aims: The aim of the present study was to compare the results of HER-2/neu expression using routine immunohistochemistry method LSAB ® + (Dakocytomation polyclonal antibody A0485) and HercepTest ® . Material and methods: 50 cases of breast carcinoma previously evaluated for HER-2/neu expression by routine immunohistochemistry using the LSAB+ method were included. These cases were also evaluated for HER-2/neu expression using HercepTest ® for comparison. Results: 34 cases of breast carcinoma were negative for HER-2/neu expression by the two...
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