Lesões mamárias felinas: contributo para a sua caracterização biopatológica
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Data
2004
Autores
Travassos, Fernanda Aurora Gomes de Seixas
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Resumo
De entre as neoplasias da mama da gata, os carcinomas são os mais frequentes, sendo reconhecidos pela sua alta agressividade biológica e mau prognóstico. Tendo em conta a escassez de critérios morfológicos e biológicos com valor prognóstico comprovado para estas neoplasias, pretendemos com este estudo, contribuir à identificação dos factores mais significativos para avaliar o comportamento mais ou menos agressivo destas neoplasias. Foi ainda objectivo major melhorar o sistema de classificação histológica existente, dadas as suas insuficiências práticas de aplicação universal e reprodutível.
Foram analisados 130 nódulos mamários, caracterizados de acordo com a frequência e com os parâmetros clinico-patológicos. Para a caracterização das lesões recorremos à histologia convencional, a técnicas de coloração e imuno-histoquímica para a vimentina, marcadores de diferenciação mioepitelial (CK14, p63, calponina), caderina E e β-catenina, MMP1, MMP2, TIMP1, VEGF, HER-2/neu; foi ainda efectuado o estudo da ploidia de ADN e parâmetros associados. Foi também realizado um estudo de seguimento para aferir melhor os parâmetros de prognóstico em análise uni e multivariada.
Os carcinomas de mama surgiram principalmente em gatas de idade média a avançada e apresentaram aspectos macro e microscópicos diversos. Além de carcinomas ductais sem características específicas, foram identificados grupos de carcinomas invasores com características bifásicas (carcinomas epiteliais-mioepiteliais), com elementos metaplásicos, epidermóides e/ou heterólogos (carcinomas metaplásicos) e com predomínio do padrão micropapilar (carcinoma micropapilar). O carcinoma epitelial-mioepitelial evidenciou características de baixa agressividade biológica: baixo grau histológico e nuclear, índices proliferativos baixos, fenótipo preservado de caderina E e β-catenina, baixa expressão de MMP1, TIMP1, VEGF, HER-2, conteúdo de ADN diplóide e os melhores tempos de sobrevivência livre de doença e total. Por oposição salientaram-se os carcinomas metaplásicos e micropapilares, associados a critérios histológicos clássicos de agressividade biológica, fenótipo reduzido das moléculas de adesão, expressão alta dos marcadores imunohistoquímicos, conteúdo de ADN aberrante e baixos tempos de sobrevivência. Os carcinomas invasores sem tipo específico revelaram-se um grupo heterogéneo, com características histológicas, imuno-histoquímicas, ploidia de ADN e tempos de sobrevivência variáveis.
Foram critérios de prognóstico independente para a sobrevivência total o grau histológico e a ocorrência de metástases no momento da exérese e, para a sobrevivência livre de doença o grau histológico e a permeação vascular. No grupo das gatas sem VIII metástases ganglionares (N0) foram critérios de prognóstico independente o tamanho, o tipo e o grau histológico, com as gatas com carcinomas metaplásicos e micropapilares a evidenciarem um aumento substancial de risco de morte por doença oncológica.
Estes resultados demonstram claramente que existem tipos histológicos de carcinomas com agressividade biológica distinta, que devem ser incluídos na classificação dos carcinomas da gata. Demonstram ainda a importância da graduação histológica na avaliação destas neoplasias.
Carcinomas are the most frequent neoplasia of feline mammary gland, known for its biological aggressiveness and bad prognosis. The prognostic value of morphologic and biological parameters in this species is unknown; therefore, the objective of this study was to identify the factors that affect the behaviour and natural history of feline neoplasias. Additionally, since there is no universal consensus regarding the current Word Health Organization classification of feline mammary tumours, we propose a new classification system. The frequency and clinicopathological parameters of 130 mammary nodules were observed and classified. Mammary changes and neoplasias were characterized using conventional histology, histochemistry and immunohistochemistry techniques using antibodies against vimentin, myoepitelial markers (CK14, p63, calponin), E-cadherin and β-catenin, MMP1, MMP2, TIMP1, VEGF, HER-2/neu; we also evaluated the nuclear DNA content and associated cytometric parameters. A disease-free survival and overall survival using univariate and multivariate analysis were conducted in order to determine the effect of the clinicopathological parameters in the prognosis. Carcinomas affected mainly middle age to elderly females and presented variable macro and microscopical features. We identified invasive ductal carcinoma of not otherwise specified type (ductal NOS), and specific types of tumours: biphasic carcinomas (epithelialmyoepithelial carcinomas), metaplastic carcinomas (presenting squamous and/or heterologous mesenchymal differentiation), and micropapillary carcinomas. Epithelial-mioepitelial carcinoma were associated to histologic features of low biological aggressiveness: they were low grade, low proliferating tumours, with scanty nuclear pleomorphism, preserved phenotype of E-cadherin and β-catenin, and low immunoexpression rates of MMP1, TIMP1, VEGF, HER-2. Most lesions were DNA diploid. This tumour type presented good disease-free survival and overall survival. On the other hand, metaplastic and micropapillary carcinomas were more likely to be poorly differentiated, and to behave aggressively; they presented reduced levels of adhesion molecules, high immunorreactivity indices, abnormal DNA content and low overall survival and disease-free survival. Ductal NOS was a heterogeneous tumour group, presenting diverse histology, immunohistochemistry pattern, and DNA ploidy. The overall survival and disease-free survival were also variable. In multivariate analysis the traditional pathological parameters of lymph node status, tumour size, histological type, and histological grade were the most useful prognostic factors: histological grade and lymph node status had independent significance for overall survival; histological grade and lymphovascular invasion achieved statistical significance for disease-free survival. In lymph node negative queens, larger size, histological type and high histological grade were associated with an adverse outcome. Among the histological types, metaplastic and micropapillary carcinomas exhibited a more aggressive behaviour and a greater risk of death by mammary cancer than the other types of tumours. These results clearly demonstrate that these histological types have diverse degrees of biological aggressiveness; thus they should be included in a new classification system of the feline mammary lesions. They also prove histological grade to be a reliable prognostic factor, identifying queens at greater risk of lymph node involvement and an adverse outcome.
Carcinomas are the most frequent neoplasia of feline mammary gland, known for its biological aggressiveness and bad prognosis. The prognostic value of morphologic and biological parameters in this species is unknown; therefore, the objective of this study was to identify the factors that affect the behaviour and natural history of feline neoplasias. Additionally, since there is no universal consensus regarding the current Word Health Organization classification of feline mammary tumours, we propose a new classification system. The frequency and clinicopathological parameters of 130 mammary nodules were observed and classified. Mammary changes and neoplasias were characterized using conventional histology, histochemistry and immunohistochemistry techniques using antibodies against vimentin, myoepitelial markers (CK14, p63, calponin), E-cadherin and β-catenin, MMP1, MMP2, TIMP1, VEGF, HER-2/neu; we also evaluated the nuclear DNA content and associated cytometric parameters. A disease-free survival and overall survival using univariate and multivariate analysis were conducted in order to determine the effect of the clinicopathological parameters in the prognosis. Carcinomas affected mainly middle age to elderly females and presented variable macro and microscopical features. We identified invasive ductal carcinoma of not otherwise specified type (ductal NOS), and specific types of tumours: biphasic carcinomas (epithelialmyoepithelial carcinomas), metaplastic carcinomas (presenting squamous and/or heterologous mesenchymal differentiation), and micropapillary carcinomas. Epithelial-mioepitelial carcinoma were associated to histologic features of low biological aggressiveness: they were low grade, low proliferating tumours, with scanty nuclear pleomorphism, preserved phenotype of E-cadherin and β-catenin, and low immunoexpression rates of MMP1, TIMP1, VEGF, HER-2. Most lesions were DNA diploid. This tumour type presented good disease-free survival and overall survival. On the other hand, metaplastic and micropapillary carcinomas were more likely to be poorly differentiated, and to behave aggressively; they presented reduced levels of adhesion molecules, high immunorreactivity indices, abnormal DNA content and low overall survival and disease-free survival. Ductal NOS was a heterogeneous tumour group, presenting diverse histology, immunohistochemistry pattern, and DNA ploidy. The overall survival and disease-free survival were also variable. In multivariate analysis the traditional pathological parameters of lymph node status, tumour size, histological type, and histological grade were the most useful prognostic factors: histological grade and lymph node status had independent significance for overall survival; histological grade and lymphovascular invasion achieved statistical significance for disease-free survival. In lymph node negative queens, larger size, histological type and high histological grade were associated with an adverse outcome. Among the histological types, metaplastic and micropapillary carcinomas exhibited a more aggressive behaviour and a greater risk of death by mammary cancer than the other types of tumours. These results clearly demonstrate that these histological types have diverse degrees of biological aggressiveness; thus they should be included in a new classification system of the feline mammary lesions. They also prove histological grade to be a reliable prognostic factor, identifying queens at greater risk of lymph node involvement and an adverse outcome.
Descrição
Tese de Doutoramento em Ciências Veterinárias
Palavras-chave
Medicina veterinária , Gato , Oncologia , Neoplasias mamárias , Lesões (mamárias) , Imunohistoquímica , Biologia mulecular , Citometria