Avaliação da imunoexpressão do receptor 2 do fator de crescimento epidérmico humano (HER2) e do antígeno nuclear Ki67 no carcinoma de saco anal canino
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Data
2022-07-11
Autores
Paiva, Felipe Noleto de
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Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma de saco anal é uma neoplasia marcada por comportamento agressivo, com diversas formas de terapia relatadas. A cirurgia permanece como tratamento de eleição, sendo, no entanto, controversa em casos avançados e com metástase instalada. Os fatores prognósticos conhecidos, são igualmente controversos, e dessa forma, novos estudos têm sido realizados buscando novos marcadores prognósticos e preditivos. O HER2 é uma proteína de membrana relacionada ao processo de tumorigênese, comprovadamente expressa em diferentes tipos tumorais, na medicina humana e veterinária. O Ki67, por sua vez, é uma proteína nuclear, com função relacionada à proliferação celular que atua, como importante marcador prognóstico no câncer. O objetivo do presente trabalho foi avaliar a imunoexpressão dos marcadores HER2 e Ki67 em casos de carcinoma de saco anal canino. Inicialmente foi realizado um estudo retrospectivo, acerca do carcinoma de saco anal em caninos, com um N de 260 casos. Posteriormente, foram obtidas amostras de carcinoma de saco anal, incluídas em parafina, junto ao laboratório parceiro, divididas em quatro grupos: maior diâmetro tumoral menor que 2,5cm, maior diâmetro tumoral maior que 2,5cm, linfonodos metastáticos e grupo controle. Cada grupo foi representado por um N de 10 amostras, sendo então realizada imunomarcação para os marcadores HER2 e Ki67. Foi encontrado um maior acometimento em animais adultos a idosos, do sexo feminino e sem raça definida. Em relação ao tamanho tumoral, observou-se que os tumores frequentemente são diagnosticados já com dimensões elevadas. Quanto a avaliação imunoistoquímica, a marcação de HER2 foi positiva em 45% dos casos de tumor primário, com marcação 100% negativa no grupo controle, composto por amostras de saco anal íntegro. A imunoexpressão do Ki67 teve mediana de 25% em todos os grupos avaliados, com exceção do grupo controle, com mediana de 8% de imunoexpressão. Não houve associação entre a imunoexpressão do HER2 ou do Ki67 nos diferentes tamanhos tumorais, nem na comparação de tumores primários e metastáticos. O estudo demonstrou que a imunoexpressão do HER2 e do Ki67 está presente em carcinomas de saco anal, representando um potencial alvo terapêutico, diferindo dos sacos anais não neoplásicos.
Anal sac carcinoma is a neoplasm marked by aggressive behavior, with several forms of therapy reported. Surgery remains the treatment of choice, although it is controversial in advanced cases with established metastasis. The known prognostic factors are equally controversial, and thus, new studies have been carried out looking for new prognostic and predictive markers. HER2 is a membrane protein related to the tumorigenesis process, proven to be expressed in different tumor types in Human and Veterinary Medicine. Ki67 is a nuclear protein, with function related to cell proliferation that acts as an important prognostic marker in cancer. The aim of the present study was to evaluate the immunoexpression of HER2 and Ki67 markers in cases of canine anal sac carcinoma. Initially, a retrospective study was carried out on anal sac carcinoma in canines, with an N of 260 cases. Subsequently, samples of anal sac carcinoma, embedded in paraffin, were obtained from the partner laboratory, divided into four groups: largest tumor diameter less than 2.5 cm, largest tumor diameter greater than 2.5 cm, metastatic lymph nodes and control group. Each group was represented by an N of 10 samples, and immunostaining for markers HER2 and Ki67 was then performed. A greater involvement was found in adult to elderly animals, female and mixed breed. Regarding the tumor size, it was observed that tumors are often diagnosed with high dimensions. As for the immunohistochemical evaluation, HER2 staining was positive in 45% of the primary tumor cases, with 100% negative staining in the control group, composed of intact anal sac samples. Ki67 immunoexpression had a median of 25% in all groups evaluated, with the exception of the control group, with a median of 8% immunoexpression. There was no association between HER2 or Ki67 immunoexpression in different tumor sizes, nor in the comparison of primary and metastatic tumors. The study demonstrated that HER2 and Ki67 immunoexpression is present in anal sac carcinomas, representing a potential therapeutic target, differing from non-neoplastic anal sacs.
Anal sac carcinoma is a neoplasm marked by aggressive behavior, with several forms of therapy reported. Surgery remains the treatment of choice, although it is controversial in advanced cases with established metastasis. The known prognostic factors are equally controversial, and thus, new studies have been carried out looking for new prognostic and predictive markers. HER2 is a membrane protein related to the tumorigenesis process, proven to be expressed in different tumor types in Human and Veterinary Medicine. Ki67 is a nuclear protein, with function related to cell proliferation that acts as an important prognostic marker in cancer. The aim of the present study was to evaluate the immunoexpression of HER2 and Ki67 markers in cases of canine anal sac carcinoma. Initially, a retrospective study was carried out on anal sac carcinoma in canines, with an N of 260 cases. Subsequently, samples of anal sac carcinoma, embedded in paraffin, were obtained from the partner laboratory, divided into four groups: largest tumor diameter less than 2.5 cm, largest tumor diameter greater than 2.5 cm, metastatic lymph nodes and control group. Each group was represented by an N of 10 samples, and immunostaining for markers HER2 and Ki67 was then performed. A greater involvement was found in adult to elderly animals, female and mixed breed. Regarding the tumor size, it was observed that tumors are often diagnosed with high dimensions. As for the immunohistochemical evaluation, HER2 staining was positive in 45% of the primary tumor cases, with 100% negative staining in the control group, composed of intact anal sac samples. Ki67 immunoexpression had a median of 25% in all groups evaluated, with the exception of the control group, with a median of 8% immunoexpression. There was no association between HER2 or Ki67 immunoexpression in different tumor sizes, nor in the comparison of primary and metastatic tumors. The study demonstrated that HER2 and Ki67 immunoexpression is present in anal sac carcinomas, representing a potential therapeutic target, differing from non-neoplastic anal sacs.
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Medicina Veterinária, Imuno-histoquímica, Câncer, Cão