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Estudo da expressão das proteínas Rab11a e Rab11b em cancro da mama ductal invasivo
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Advisor(s)
Abstract(s)
O cancro da mama é o mais prevalente em mulheres e o segundo mais mortal depois do cancro do pulmão. Desta forma, existe interesse no estudo deste cancro para melhorar a qualidade de vida e aumentar a esperança livre da doença das pacientes. Este cancro é muito heterogéneo e existem diferentes subtipos moleculares identificados, nomeadamente o basal-like, triplo negativo, Luminal A, Luminal B e o HER2. Pode ter diferentes origens como a hereditária, genes BRCA 1 e BRCA 2, intracelular que pode levar a alterações das vias de sinalização como a do Ras e alterações nos recetores hormonais como o do estrogénio, progesterona e HER2.
Neste trabalho o objetivo principal foi o estudo da expressão das proteínas Rab11a e Rab11b. Para tal fez-se a comparação da expressão destas proteínas na mama normal com os carcinomas ductal in situ (CDIS) e invasivo (CDI). Estabeleceu-se um protocolo com o Hospital Beatriz Ângelo que forneceu 99 blocos de amostras em parafina os quais foram submetidos à imunohistoquímica e os resultados da expressão foram analisados visualmente por dois avaliadores independentes e baseou-se numa escala que avaliou a expressão da proteína e a classificou entre 0 e 3. O resultado final foi confirmado pelo software ImageJ.
Nos resultados obtidos observámos que a expressão das proteínas na mama normal é elevada, mas esta diminui no estado inicial do tumor (CDIS) e diminui acentuadamente quando o tumor se torna mais agressivo e indiferenciado; nos resultados da comparação da expressão na mama normal com os subtipos luminal A e luminal B observámos também a diminuição da expressão da Rab11a e da Rab11b da mama normal para os subtipos. Ambos os resultados indicam um possível comportamento destas Rabs como supressoras tumorais na mama normal e como tal potenciais biomarcadores no CDI.
Breast cancer is the most prevalent in women and the second most deadly after lung cancer. There is interest in the study of this cancer to improve the quality of life and increase the disease-free hope of the patients. This cancer is very heterogeneous and there are different molecular subtypes identified, namely basal-like, triple negative, Luminal A, Luminal B and HER2. It can have different origins as the hereditary one, by the genes BRCA 1 and BRCA 2; which may lead to changes in signaling pathways such as Ras and alterations in hormone receptors such as estrogen, progesterone and HER2. In this project the main goal was to study the expression of Rab11a and Rab11b. proteins in the breast invasive ductal carcinoma and to correlate the expression with clinical and histological data. For this purpose, we had a protocol with the Hospital Beatriz Ângelo which sent us 99 blocks of samples in paraffin, being all of them evaluated by immunohistochemistry (IHC) and the expression results were analyzed visually by two independent evaluators and was based on a visual scale that determines the expression of the protein and ranks it between 0-3. The final result is confirmed by ImageJ software. The results indicate that the protein expression in normal breast is high, but decreases in the initial state of the tumor (DCIS) and decreases sharply when the tumor becomes more aggressive and undifferentiated; in the comparison of the expression in the normal breast with the subtypes luminal A and luminal B, we also observed a decrease of Rab11a and Rab11b expression in the normal breast to the subtypes. Both results indicate a possible behaviour of these Rabs as a tumor suppressor in the normal breast and as such potential biomarkers in the IDC.
Breast cancer is the most prevalent in women and the second most deadly after lung cancer. There is interest in the study of this cancer to improve the quality of life and increase the disease-free hope of the patients. This cancer is very heterogeneous and there are different molecular subtypes identified, namely basal-like, triple negative, Luminal A, Luminal B and HER2. It can have different origins as the hereditary one, by the genes BRCA 1 and BRCA 2; which may lead to changes in signaling pathways such as Ras and alterations in hormone receptors such as estrogen, progesterone and HER2. In this project the main goal was to study the expression of Rab11a and Rab11b. proteins in the breast invasive ductal carcinoma and to correlate the expression with clinical and histological data. For this purpose, we had a protocol with the Hospital Beatriz Ângelo which sent us 99 blocks of samples in paraffin, being all of them evaluated by immunohistochemistry (IHC) and the expression results were analyzed visually by two independent evaluators and was based on a visual scale that determines the expression of the protein and ranks it between 0-3. The final result is confirmed by ImageJ software. The results indicate that the protein expression in normal breast is high, but decreases in the initial state of the tumor (DCIS) and decreases sharply when the tumor becomes more aggressive and undifferentiated; in the comparison of the expression in the normal breast with the subtypes luminal A and luminal B, we also observed a decrease of Rab11a and Rab11b expression in the normal breast to the subtypes. Both results indicate a possible behaviour of these Rabs as a tumor suppressor in the normal breast and as such potential biomarkers in the IDC.
Description
Keywords
Carcinoma ductal invasivo Rab11a Rab11b Imunohistoquímica (IHQ) ImageJ