Estudo da expressão imuno-histoquímica dos recetores de TGF-β em lesões neoplásicas de mama de cadela
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2018-01-08
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As neoplasias mamárias são as neoplasias mais frequentes em cadelas inteiras, sendo metade delas malignas. As suas características semelhantes, fazem com que sejam um bom modelo de estudo para o cancro da mama da mulher. O Fator de Crescimento de Transformação β (TGFβ) é uma citoquina com importância relevante no desenvolvimento e diferenciação celular, regulação da proliferação epitelial, bem como na reparação de ADN, estimulação da apoptose e função das células estaminais, na maioria dos tecidos. Em epitélio normal e em lesões pré-neoplásicas, o TGFβ é responsável pela inibição do crescimento celular atuando como promotor da diferenciação celular e apoptose, estando associado a um melhor prognóstico. Em fases mais avançadas, existe um silenciamento dos seus efeitos supressores, entrando em cena os efeitos promotores neoplásicos, como a evasão à imunovigilância, o aumento da mobilidade celular e a metastização, estando associado a um pior prognóstico. A maioria das células medeiam a sinalização do TGFβ através dos recetores tipo 1, 2 e 3 do TGFβ (TGFβRI, TGFβRII e TGFβRIII, respetivamente). As mutações/alterações mais comumente associadas à diminuição ou perda total de sinalização do TGFβ, e que podem estar associadas a fenómenos de progressão tumoral, são frequentemente relacionadas com os recetores 1 e 2. A realização deste trabalho tem como objetivo principal, contribuir para uma melhor caracterização biopatológica das neoplasias mamárias caninas, especificamente quanto à expressão imuno-histoquímica dos recetores de tipo 1 e 2 do TGFβ em tecidos mamários sãos e em neoplasias benignas e malignas, bem como nas glândulas mamárias adjacentes. Encontrou-se uma relação entre a expressão estromal de TGFβRI e os grupos histológicos avaliados (p<0,0001),tendo as neoplasias benignas e os carcinomas invasores apresentado expressão significativamente menor (92,3% e 75% respetivamente de baixa expressão) do que as amostras sem alterações neoplásicas (75% de alta expressão). Também se encontrou uma relação entre a expressão estromal de TGFβRI e o grau histológico (p=0,027). A elevada expressão epitelial e a baixa expressão estromal de TGFβRII encontrouse significativamente associada com a presença de invasão vascular, observando-se uma relação próxima da significância, com a metástase ganglionar. Neste modelo, parece consistente a relação entre a variação da expressão dos recetores do TGFβ e a manifestação de características de malignidade, sendo necessários estudos futuros que comprovem estes resultados.
Mammary tumors are the most frequent neoplasms in non-spayed bitches, half of which are malignant. Their similar characteristics make them a good model for women breast cancer. Transforming growth factor β (TGFβ) is a cytokine that plays a determinant role in cell development and differentiation, in the regulation of epithelial proliferation, as well as in the ability to mediate damaged DNA repair, stimulation of apoptosis and stem cell function in most cell tissues. In normal epithelium and pre-neoplastic lesions, TGFβ is responsible for cell growth inhibition, cell differentiation and apoptosis, being in such cases associated with a better prognosis. In more advanced stages of neoplastic progression, there is a silencing of its suppressive effects of growth and apoptosis, by functional mutation/inactivation of the receptors or corruption of downstream pathways, with neoplastic promoter effects such as immunosurveillance avoidance, increased cell mobility and metastasis, being associated, in such cases, with a worse prognosis. The vast majority of cells mediate TGFβ signaling through 3 receptors: TGFβ type 1, 2 and 3 receptors (TGFβRI, TGFβRII and TGFβRIII, respectively). The mutations or alterations in expression most commonly associated with the decrease or total loss of TGFβ signaling, and which may potentially be associated with tumor progression, are frequently related to receptors 1 and 2. The main objective of this work is to contribute to a better biopathological characterization of canine mammary tumors, specifically regarding the immunohistochemical expression of TGFβ type 1 and 2 receptors in normal canine mammary tissues and in benign and malignant neoplasms, as well as in the adjacent mammary glands. A relationship was found between stromal expression of TGFβRI and the histological groups evaluated (p <0.0001) with benign neoplasms and invasive carcinomas being significantly characterized by low expression (92.3% and 75%, respectively) when compared to samples without neoplastic changes (75% of high expression). A relationship was also found between stromal expression of TGFβRI and histological grade (p = 0.027). High epithelial expression, and low stromal expression of TGFβRII were significantly associated with the presence of vascular invasion, and a tendency to significance was observed with lymph node metastasis. The relationship between the variation of TGFβ receptor expression and the manifestation of malignancy characteristics seems consistent; additional studies with larger series are welcome to confirm our results.
Mammary tumors are the most frequent neoplasms in non-spayed bitches, half of which are malignant. Their similar characteristics make them a good model for women breast cancer. Transforming growth factor β (TGFβ) is a cytokine that plays a determinant role in cell development and differentiation, in the regulation of epithelial proliferation, as well as in the ability to mediate damaged DNA repair, stimulation of apoptosis and stem cell function in most cell tissues. In normal epithelium and pre-neoplastic lesions, TGFβ is responsible for cell growth inhibition, cell differentiation and apoptosis, being in such cases associated with a better prognosis. In more advanced stages of neoplastic progression, there is a silencing of its suppressive effects of growth and apoptosis, by functional mutation/inactivation of the receptors or corruption of downstream pathways, with neoplastic promoter effects such as immunosurveillance avoidance, increased cell mobility and metastasis, being associated, in such cases, with a worse prognosis. The vast majority of cells mediate TGFβ signaling through 3 receptors: TGFβ type 1, 2 and 3 receptors (TGFβRI, TGFβRII and TGFβRIII, respectively). The mutations or alterations in expression most commonly associated with the decrease or total loss of TGFβ signaling, and which may potentially be associated with tumor progression, are frequently related to receptors 1 and 2. The main objective of this work is to contribute to a better biopathological characterization of canine mammary tumors, specifically regarding the immunohistochemical expression of TGFβ type 1 and 2 receptors in normal canine mammary tissues and in benign and malignant neoplasms, as well as in the adjacent mammary glands. A relationship was found between stromal expression of TGFβRI and the histological groups evaluated (p <0.0001) with benign neoplasms and invasive carcinomas being significantly characterized by low expression (92.3% and 75%, respectively) when compared to samples without neoplastic changes (75% of high expression). A relationship was also found between stromal expression of TGFβRI and histological grade (p = 0.027). High epithelial expression, and low stromal expression of TGFβRII were significantly associated with the presence of vascular invasion, and a tendency to significance was observed with lymph node metastasis. The relationship between the variation of TGFβ receptor expression and the manifestation of malignancy characteristics seems consistent; additional studies with larger series are welcome to confirm our results.
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Neoplasia mamária , cadela , imuno-histoquímica , TGFβ , TGFβRI , TGFβRII