Avaliação da expressão dos genes TGFBR1 e TGFBR2 em amostras de carcinomas ductais invasivos
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Data
2008-02-28
Autores
Paiva, Carlos Eduardo [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O câncer de mama (CM) ocupa o primeiro lugar em incidência e o segundo em mortalidade entre as mulheres no mundo. É considerada uma doença heterogênea com alterações em diversas vias de sinalização molecular. Os fatores prognósticos atuais são incapazes de predizer a evolução da totalidade dos pacientes, assim como os marcadores preditivos não conseguem evitar que grande parte das pacientes com CM sejam submetidas à tratamento desnecessário. A busca de outros marcadores tumorais, tanto prognósticos quanto preditivos tem sido alvo de inúmeras pesquisas, que buscam predizer a evolução clínica de um número maior de pacientes. Dois marcadores tumorais com possíveis implicações clínicas são o TGFB1 e o seu receptor TGFBR2. No entanto, o papel do TGFB1 na carcinogênese e na progressão do câncer de mama ainda não é totalmente conhecido. Desta forma, o objetivo deste estudo foi avaliar a expressão do TGFB1 e do TGFBR2 em tumores de mama e correlacionar com os dados clínicos e histopatológicos. Para tanto, foram analisadas 49 amostras de carcinomas ductais invasivos primários e sete amostras de mamas normais como controles pelas técnicas de RT-PCR quantitativa em tempo real (qRTPCR) e imunohistoquímica (IHQ). Os resultados mostraram que baixos níveis de expressão protéica de TGFB1 nas células tumorais estavam associados a menor sobrevida livre de doença. Os tumores apresentaram acentuada diminuição da expressão do transcrito TGFBR2 quando comparados ao controle normal. Além disso, foram observados baixos níveis dos transcritos TGFB1 e TGFBR2 nos tumores com fenótipos mais agressivos (alto índice proliferativo e estadio avançado). Esses dados sugerem que o TGFB1 atua como supressor tumoral em CMs e que a diminuição da expressão TGFB1 e TGFBR2 é um evento importante na carcinogênese mamária. A detecção dos níveis de expressão protéica...
Breast cancer (BC) is the leading female cancer in incidence and the second one in mortality worldwide. BC is considered a heterogeneous disease, that presents abnormalities in several molecular pathways. The known prognostic markers are not capable to predict the outcome of all the patients, as well as the predictive markers are not capable to avoid unnecessary treatments. It is necessary to search for other tumor markers, even prognostic and predictive, regarding the prediction of a higher number of patient’s outcome. Two tumor markers with possible clinical implications are TGFB1 and its receptor TGFBR2. However the role of TGFB1 in carcinogenesis and in the BC progression is not totally understood yet. In this way, the aim of this study was to analyze the expression of TGFB1 and TGFBR2 in breast tumors and to correlate it with clinical and histopathological data. For this, it were analyzed 49 ductal invasive carcinomas and 7 normal breast tissues as controls with quantitative real time PCR (qRT-PCR) and immunohistochemistry (IHC) technologies. The results showed that low expression levels of TGFB1 protein in tumor cells were associated with a lower disease-free survival. Tumors presented highly diminished TGFBR2 transcript expression when compared with normal controls. Moreover, low levels of TGFB1 and TGFBR2 transcripts were observed in tumors with aggressive phenotypes (high proliferation index and advanced stage). These results suggests that TGFB1 acts like a tumor supressor in BCs and that the TGFB1 and TGFBR2 lowering expression is an important event in mammary carcinogenesis. The detection of tumor TGFB1 protein expression levels can be helpful in clinical practice like a prognostic marker in mammary carcinomas.
Breast cancer (BC) is the leading female cancer in incidence and the second one in mortality worldwide. BC is considered a heterogeneous disease, that presents abnormalities in several molecular pathways. The known prognostic markers are not capable to predict the outcome of all the patients, as well as the predictive markers are not capable to avoid unnecessary treatments. It is necessary to search for other tumor markers, even prognostic and predictive, regarding the prediction of a higher number of patient’s outcome. Two tumor markers with possible clinical implications are TGFB1 and its receptor TGFBR2. However the role of TGFB1 in carcinogenesis and in the BC progression is not totally understood yet. In this way, the aim of this study was to analyze the expression of TGFB1 and TGFBR2 in breast tumors and to correlate it with clinical and histopathological data. For this, it were analyzed 49 ductal invasive carcinomas and 7 normal breast tissues as controls with quantitative real time PCR (qRT-PCR) and immunohistochemistry (IHC) technologies. The results showed that low expression levels of TGFB1 protein in tumor cells were associated with a lower disease-free survival. Tumors presented highly diminished TGFBR2 transcript expression when compared with normal controls. Moreover, low levels of TGFB1 and TGFBR2 transcripts were observed in tumors with aggressive phenotypes (high proliferation index and advanced stage). These results suggests that TGFB1 acts like a tumor supressor in BCs and that the TGFB1 and TGFBR2 lowering expression is an important event in mammary carcinogenesis. The detection of tumor TGFB1 protein expression levels can be helpful in clinical practice like a prognostic marker in mammary carcinomas.
Descrição
Palavras-chave
Imuno-histoquímica, Carcinogênese mamária, Mammary carcinomas
Como citar
PAIVA, Carlos Eduardo. Avaliação da expressão dos genes TGFBR1 e TGFBR2 em amostras de carcinomas ductais invasivos. 2008. 72f. Dissertação (mestrado) - Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, 2008.