Immunohistochemical expression of αB-crystallin and L1CAM in canine mammary tumors
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2017
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Resumo
Os tumores de mama representam um dos tipos de cancro mais comuns na mulher,
sendo que a cadela é apontada, atualmente, como o melhor modelo animal para o seu estudo.
Assim sendo, a investigação neste ramo tem crescido a um ritmo elevado.
A αB-cristalina (CRYAB) pertence à superfamília das small heat shock proteins,
influenciando a homeostasia celular e tendo funções anti-apoptóticas, enquanto a molécula de
adesão celular L1 (L1CAM) é uma glicoproteína de superfície da família das imunoglobulinas,
interagindo com a matriz extracelular e com outras células. Recentemente foi descrito o seu
envolvimento na angiogénese. Neste trabalho, foram realizados dois estudos
imunohistoquímicos independentes em tumores mamários caninos, tendo um avaliado a
expressão do CRYAB e o outro a expressão do L1CAM.
Para avaliar a imunoexpressão do CRYAB em tumores mamários caninos, foram
utilizadas 79 amostras, constituidas por tecidos normais/hiperplásicos (n=9), tumores benignos
(n=15) e malignos (n=55). A avaliação foi feita com base num método semi-quantitativo,
multiplicando a percentagem (PS) pela intensidade da imunomarcação (SI), obtendo o score
total (PSxSI), posteriormente dividido em score alto (TS≥4) e baixo (TS<4). Os resultados
revelaram uma baixa expressão do CRYAB ao nível do mioepitélio das amostras normais/
hiperplásicas e uma maior expressão em amostras tumorais. Encontrámos diferenças
estatisticamente significativas relativamente à expressão do CRYAB entre diferentes grupos
histológicos (p=0.022) e entre os diferentes tipos histológicos de neoplasias malignas, sendo
mais frequentemente expresso em neoplasias com proliferação mioepitelial. A expressão do
CRYAB encontrava-se também associada à ausência de metástases nos linfonodos
(p=0.014). Consideramos necessários estudos com uma amostragem maior para confirmar as
diferenças obtidas.
A expressão do L1CAM foi avaliada em 27 carcinomas mamários de alto grau
histológico, incluindo 12 carcinomas inflamatórios e 15 não inflamatórios. A avaliação foi
efetuada baseando-se na percentagem e intensidade de células coradas (PS e SI,
respetivamente). O score final foi obtido somando PS+SI, obtendo valores 0 ou 2 a 8. O
objetivo foi avaliar se existiam diferenças na expressão do L1CAM entre carcinomas
inflamatórios e não inflamatórios. Os resultados revelaram diferenças entre o grupo
inflamatório e o não inflamatório (p=0.003), com uma sobrexpressão no grupo inflamatório.
O padrão de coloração apresentado pelas células também se revelou
significativamente diferente (p=0.036). Relativamente às células endoteliais,
encontrámos uma correlação positiva entre a expressão do L1CAM e a positividade de células
endoteliais do tumor e do endotélio com êmbolos, mas não a níveis significativos (p=0.05).
Na vasculatura normal, observou-se sobrexpressão do L1CAM relativamente às
células endoteliais do tumor, com 56% (n=14) das mesmas com expressão
negativa. Estes resultados revelam, pela primeira vez em tumores mamários caninos, que
o L1CAM poderá representar um alvo terapêutico em carcinoma inflamatório, dadas as
diferenças encontradas entre os dois grupos. São necessários estudos posteriores, em
séries mais numerosas, para reunir mais informação acerca desta molécula.
Human breast cancer is one of the most common neoplasms found in women, being the female dog the most accurate animal model to study it. Research on this field has been growing largely for the past years. αB-Crystallin (CRYAB) is a member of the small heat shock proteins superfamily, implicated in cellular homeostasis and anti-apoptotic features, while L1 cell adhesion molecule (L1CAM) is a surface glycoprotein of the Ig’s superfamily interacting with the extracellular matrix and other cells and more recently implicated in angiogenesis. In the present work, two separate immunohistochemical studies were performed in canine mammary tumors, one evaluating CRYAB and the other L1CAM expression. To evaluate CRYAB expression in canine mammary tumors (CMT’s) we used a series of 79 samples, composed by normal/hyperplastic tissues (n=9), benign tumors (n=15) and malignant tumors (n=55). Immunohistochemical evaluation was based on a semiquantitative analysis, according to the immunolabeling percentage (PS) and staining intensity (SI). A final score was obtained, based on the product PSxSI, with tissues classified as low (PSxSI<4) or high scores (PSxSI≥4). The goal was to evaluate the immunolabeling characteristics and to accomplish if there was any relation of CRYAB expression and clinicopathological characteristics, such as lymph-node metastasis or histological groups. Results showed a low expression of CRYAB by the myoepithelium of normal/hyperplastic tissues and a tendency to a higher expression in tumors (either benign or malignant), although not on a significant level. We found significant differences between histological groups regarding CRYAB expression (p=0.022). Positive expression was associated with the absence of lymphnode metastasis (p=0.014). CRYAB was mainly expressed by the myoepithelial cells of tumor samples, although not exclusively. Differences between histological groups suggest CRYAB may be a future factor of prognosis and probably an interesting therapeutic target. Further studies with a larger series are required to explain the differences obtained. L1CAM expression was evaluated on 27 malignant, grade 3 CMT’s, including inflammatory carcinomas (n=12) and non-inflammatory carcinomas (n=15). Immunohistochemical evaluation was based on a quantitative analysis, according to the immunolabeling percentage (PS) and the staining intensity (SI). A final score was obtained, rising from 0 or 2 to 8, by adding PS+SI. The goal was to evaluate the differences between inflammatory and non-inflammatory carcinomas. We also evaluated L1CAM expression by endothelial cells. Results showed significant differences between the inflammatory and the non-inflammatory group (p=0.003), with an overexpression within the inflammatory group. The staining pattern was also significantly different (p=0.036). Regarding the endothelial cells, a positive correlation was found between the total score of L1CAM and the positivity of tumor and embolized vessels, but not on a significant level (p=0.05). Endothelial cells of normal vasculature showed an overexpression when compared to tumor ones. The latter showed 56% negativity in L1CAM expression (n=14). These results reveal, for the first time in CMT’s, that L1CAM may be a potential therapeutic target in inflammatory carcinomas in female dogs, giving its differences between the two groups. Further studies should be performed in larger series to accomplish more information regarding this marker in the canine species.
Human breast cancer is one of the most common neoplasms found in women, being the female dog the most accurate animal model to study it. Research on this field has been growing largely for the past years. αB-Crystallin (CRYAB) is a member of the small heat shock proteins superfamily, implicated in cellular homeostasis and anti-apoptotic features, while L1 cell adhesion molecule (L1CAM) is a surface glycoprotein of the Ig’s superfamily interacting with the extracellular matrix and other cells and more recently implicated in angiogenesis. In the present work, two separate immunohistochemical studies were performed in canine mammary tumors, one evaluating CRYAB and the other L1CAM expression. To evaluate CRYAB expression in canine mammary tumors (CMT’s) we used a series of 79 samples, composed by normal/hyperplastic tissues (n=9), benign tumors (n=15) and malignant tumors (n=55). Immunohistochemical evaluation was based on a semiquantitative analysis, according to the immunolabeling percentage (PS) and staining intensity (SI). A final score was obtained, based on the product PSxSI, with tissues classified as low (PSxSI<4) or high scores (PSxSI≥4). The goal was to evaluate the immunolabeling characteristics and to accomplish if there was any relation of CRYAB expression and clinicopathological characteristics, such as lymph-node metastasis or histological groups. Results showed a low expression of CRYAB by the myoepithelium of normal/hyperplastic tissues and a tendency to a higher expression in tumors (either benign or malignant), although not on a significant level. We found significant differences between histological groups regarding CRYAB expression (p=0.022). Positive expression was associated with the absence of lymphnode metastasis (p=0.014). CRYAB was mainly expressed by the myoepithelial cells of tumor samples, although not exclusively. Differences between histological groups suggest CRYAB may be a future factor of prognosis and probably an interesting therapeutic target. Further studies with a larger series are required to explain the differences obtained. L1CAM expression was evaluated on 27 malignant, grade 3 CMT’s, including inflammatory carcinomas (n=12) and non-inflammatory carcinomas (n=15). Immunohistochemical evaluation was based on a quantitative analysis, according to the immunolabeling percentage (PS) and the staining intensity (SI). A final score was obtained, rising from 0 or 2 to 8, by adding PS+SI. The goal was to evaluate the differences between inflammatory and non-inflammatory carcinomas. We also evaluated L1CAM expression by endothelial cells. Results showed significant differences between the inflammatory and the non-inflammatory group (p=0.003), with an overexpression within the inflammatory group. The staining pattern was also significantly different (p=0.036). Regarding the endothelial cells, a positive correlation was found between the total score of L1CAM and the positivity of tumor and embolized vessels, but not on a significant level (p=0.05). Endothelial cells of normal vasculature showed an overexpression when compared to tumor ones. The latter showed 56% negativity in L1CAM expression (n=14). These results reveal, for the first time in CMT’s, that L1CAM may be a potential therapeutic target in inflammatory carcinomas in female dogs, giving its differences between the two groups. Further studies should be performed in larger series to accomplish more information regarding this marker in the canine species.
Descrição
Dissertação de Mestrado Integrado em Medicina Veterinária
Palavras-chave
Neoplasias mamárias animais , Imunohistoquímica , Proteínas de choque térmico , Cão , αB-cristalina