Estudo citofotométrico da expressão do marcador tumoral Fator VIII e fatores prognósticos no adenocarcinoma gástrico / Cytophotometric study of the expression of the tumoral marker Factor VIII and prognostic factors in gastrci adenocarcinoma

RESUMO

RACIONAL: No câncer gástrico, a incidência, o diagnóstico e as opções terapêuticas apresentaram melhorias nas últimas décadas, porém o prognóstico permanece reservado, especialmente devido à maioria dos pacientes procurarem recurso médico com tumores avançados, metastáticos ou cirurgicamente irressecáveis já no diagnóstico. Biologia molecular é área de conhecimento recente com grandes questionamentos a serem respondidos e a atualidade dos fatos científicos mostra que o caminho deverá ser através da identificação de marcadores tumorais. Os grandes avanços na área da informática aprimoraram a análise da imagem celular através da citofotometria de imagem que possibilita através da imunoistoquímica estudar a proliferação celular e a angiogênese que participa em diversos processos tumorais, sendo pesquisadas por vários marcadores. Atualmente estudos são realizados para demonstrar o valor prognóstico de suas expressões, contudo, no adenocarcinoma gástrico resultados têm sido divergentes e estudos escassos. OBJETIVOS: Identificar e quantificar citofotometricamente a expressão dos marcadores da angiogênese através do fator VIII no adenocarcinoma e comparar suas expressões com fa classificação de Bormann, profundidade de invasão tumoral, grau de diferenciação, envolvimento nodal, padrão histológico e idade. MÉTODOS: Foram estudados 21 pacientes com adenocarcinoma gástrico, identificados de 1998 a 2006. Para a detecção do Fator VIII foi realizada imunoistoquímica, com anticorpo policlonal para Fator VIII. Foi realizada análise citofotométrica informatizada pelo sistema SAMBA 4000. RESULTADOS: Dos 21 pacientes 61,90% eram do sexo masculino e 38,10% do feminino, com idade mediana de 65 anos e apenas um não marcou para o Fator VIII (95,24% de marcação). As médias dos índices de marcagem para o Fator VIII foram de 61,14% (desvio-padrão de 15,06, variando de 29,16 a 73,91). Tumores com classificação III ou IV apresentaram índice de marcagem maiores do que aqueles com Bormann I ou II, porém sem correlação com a profundidade de invasão tumoral, grau de diferenciação, envolvimento nodal e padrão histológico. CONCLUSÕES: O presente estudo identificou e marcou 95,24% das amostras para o Fator VIII. Em relação aos fatores prognósticos não houve correlação significativa exceto entre o Fator VIII e a classificação de Bormann no qual o tipo III ou IV foi maior que o tipo I ou II.

ABSTRACT

INTRODUCTION: Regarding gastric cancer, the incidence, diagnosis and therapeutic options showed improvement in the last decades, but prognosis remains gloomy, specially due the fact that most patients, already diagnosed present advanced tumors, metastatic and not liable to be surgically resected. Molecular biology is an area in science, which can give the answer to many questions and current scientific facts show that the this should be through detection of tumoral markers. The great advances in informatics refined cell image analysis by image cytophotometry makes it possible to study cell proliferation and angiogenesis in various tumor processes using immunohistochemistry and several markers. At present, studies are conducted to demonstrate the prognostic value of their expressions, however, in gastric adenocarcinoma the results have been divergent and studies are scarce. AIM: To identify and quantify the expression of cell proliferation markers using Ki-67 and of angiogenesis with Factor VIII in gastric adenocarcinoma using cytophotometry, and compare their expressions with factors such as Bormanns´ classification, tumor invasion depth, degree of differentiation, nodal involvement, histologic pattern and age. METHODS: Twenty-one patients with gastric adenocarcinoma identified between 1998 and 2006 were studied. Ki-67 and Factor VIII expressions were performed using immunohistochemistry with clone MIB-1 primary antibodies, monoclonal for Ki-67 and policlonal for Factor VIII. Cytophotometric analysis was performed using the SAMBA 4000 system. RESULTS: Of the 21 patients 61.90% were males and 38.10% females, with a median age of 65 years. In our study eight patients had no Ki-67 marking (61,90% marking) and only one had no Factor VIII marking (95,24% marking). Means of Ki-67 labelling index was 33,25% (standard deviation 20,08, varying from 5,43 to 75,10) and of Factor VIII, 61,14% (standard deviation 15,06, varying from 29,16 to 73.91). There was no correlation between the two markers regarding gender and age. When compared between the two markers, expression for angiogenesis was significantly greater than that for cell proliferation with a mean difference between labelling index of 20,89 (p<0,001) and 15,26 standard deviation. There was no correlation between Ki-67 labelling index with comparative factors. However, regarding Factor VIII, tumors classified as III or IV present a significantly greater labelling index than those with Bormann I or II, but there was no correlation with tumor invasion depth, differentiation degree, nodal involvement and histologic pattern. CONCLUSIONS: 61,90% of the samples were identified and marked by Ki-67 and 95,24% by Factor VIII. In the marked tumors the mean Ki-67 labelling index was 33,25% and that of the Factor VIII, 61,14%. In the comparative study between the two markers, angiogenesis expression was significantly greater than that of cell proliferation. Regarding prognostic factors there was no significant correlation, except for Factor VIII and Bormanns´ classification in which type III or IV was greater than type I or II.