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Desempenho dos imunomarcadores MCM2, bcl2 e Vilina no diagnóstico diferencial de adenocarcinomas endocervicais e endometriais

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Previous issue date: 2013-10-16 / Endocervical and Endometrial Adenocarcinomas are uterine neoplasms with different biological behaviors and different treatments, being all the therapeutic plan based on the origin site of these tumors. To differentiate these two neoplasms, many times the immunohistochemical study is used as an ancillary tool to assist and complement histopathological examination. Previous studies have investigated the value of various markers in the distinction of these neoplasms, with results varying and sometimes conflicting. In this study the impact of the MCM2, bcl2 and villin markers in the differential diagnosis of endocervical and endometrial adenocarcinomas, associated or not to a traditional markers panel formed by CEA, vimentin, RE, RP and p16, was evaluated. Material and methods: A tissue microarray (TMA) was constructed using paraffin-embedded, formalin-fixed tissues from 104 hysterectomy specimens and conizations. Out of the 104, 51 samples were represented by unequivocal cases of adenocarcinomas of the endocervice and 53 represented unequivocal cases of endometrial adenocarcinomas. The sections of tissue microarray block were immunostained with the eight antibodies in study and to the antigen-antibody reaction preview it was used the polymer detection system. Scoring of immunostaining was interpreted using the German semi quantitative scoring system in considering the staining intensity and area extent of marker expression. The final Immunoreactive score was determined by multiplying the positive intensity and the positive area extent scores. The threshold for differentiating between final positive and negative immunostaining was set at 4 for interpretation (0-3 = negative; 4-12 = positive). Results: The univariate analysis showed that out of the eight markers, seven (CEA, vimentin, RE, RP, p16, MCM2 and bcl2) showed good performance in the distinction between the endocervical and endometrial origin. The multivariate analysis showed that CEA, p16 and MCM2 were the strongest predictors of site of origin. In the evaluation of six panels built by various combinations of immunomarkers , the panel with the lowest accuracy was that represented by MCM2, bcl2 and villin. The villin did not show any statistically significant difference in the differential diagnosis of these adenocarcinomas. Despite the MCM2 and bcl2 have revealed significant differences of frequency between the two sites of origin, they did not demonstrate additional benefit when added to a traditional panel. Conclusion: According to our study, the inclusion of MCM2, bcl2 and villin in the immunohistochemical assessment of uterine adenocarcinomas, added no supplementary value in the differentiation of these two neoplasms. / Adenocarcinomas endocervicais e endometriais são neoplasias uterinas com comportamentos biológicos e tratamentos distintos, sendo todo o plano terapêutico baseado no sítio de origem desses tumores. Para diferenciação dessas duas neoplasias, muitas vezes utiliza-se o estudo imuno-histoquímico como ferramenta auxiliar e complementar ao exame histopatológico. Prévios estudos têm investigado o valor de diferentes marcadores na distinção dessas neoplasias, com resultados variáveis e, por vezes, conflitantes. Neste estudo foi avaliado o desempenho dos marcadores MCM2, bcl2 e vilina no diagnóstico diferencial desses adenocarcinomas, associados ou não a um painel de marcadores tradicionais formados por CEA, vimentina, RE, RP e p16. Material e métodos: Um microarranjo de tecido (TMA) foi construído usando tecidos fixados em formol e embebidos em parafina, a partir de 104 amostras provenientes de histerectomias e conizações. Das 104 amostras, 51 eram representadas por casos inequívocos de adenocarcinomas de endocérvice e 53 representavam casos inequívocos de adenocarcinomas de endométrio. As secções do bloco de TMA foram imunomarcadas com os oito anticorpos em estudo e para vizualização da reação antígeno-anticorpo foi utilizado o sistema de detecção com polímeros. A marcação imuno-histoquímica foi graduada de acordo com o sistema semi-quantitativo alemão, levando-se em consideração a intensidade de marcação e a extensão de células marcadas. O score de imunorreatividade final foi determinado pela multiplicação da intensidade pela extensão de marcação. Um limite de corte de 4 foi determinado para diferenciação entre um resultado final positivo ou negativo (0- 3= negativo; 4- 12= positivo). Resultados: Análise univariada mostrou que dos oito marcadores avaliados, sete (CEA, vimentina, RE, RP, p16, MCM2 e bcl2) apresentaram bom desempenho na distinção entre origens endocervical e endometrial da neoplasia. Análise multivariada mostrou que CEA, p16 e MCM2 foram os mais fortes preditores do sítio anatômico. Na avaliação dos seis painéis construídos por combinações variadas desses marcadores, o painel com menor acurácia diagnóstica foi o representado por MCM2, bcl2 e vilina. A vilina não apresentou nenhuma diferença estatisticamente significativa no diagnóstico diferencial desses adenocarcinomas. Apesar do MCM2 e bcl2 terem revelado diferenças significativas de frequência entre os dois sítios de origem, eles não demonstraram valor suplementar quando adicionados a um painel tradicional. Conclusão: De acordo com este estudo, a inclusão de MCM2, bcl2 e vilina em um painel tradicional de 5 marcadores (CEA, vimentina, RE, RP, p16), não agregou nenhum benefício adicional na distinção imuno-histoquímica do sítio de origem desses adenocarcinomas uterinos.

Identiferoai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tede/3201
Date16 October 2013
CreatorsCysneiros, Maria Auxiliadora de Paula Carneiro
ContributorsMoreira, Marise Amaral Rebouças, Moreira, Marise Amaral Rebouças, Alves, Rosane R. Figueiredo, Zapata, Marco Túlio Garcia, Deus, José Miguel de
PublisherUniversidade Federal de Goiás, Programa de Pós-graduação em Ciências da Saúde (FM), UFG, Brasil, Faculdade de Medicina - FM (RG)
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguagePortuguese
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Formatapplication/pdf
Sourcereponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG
Rightshttp://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess
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