Assessment of cell proliferation and prognostic factors in canine mammary gland tumors / Avaliação da proliferação celular e fatores prognósticos em tumores mamários caninos

Three methods for the analysis of cell proliferation, mitotic index/10 high-power fields (10 HPF), mitotic index/four sets of 10 HPF (40 HPF), and MIB-1 index were evaluated in a series of canine mammary gland tumors, as well as the possible correlation between them. Fifty-six canine mammary gland tumors, including 23 benign and 33 malignant, were studied. In addition, the prognostic impact of mitotic index/10 HPF, and histological malignancy grade were evaluated in 17 malignant tumors, being seven ductal and 10 metaplastic carcinomas. The three methods used to evaluate cell proliferation were correlated with the prognostic impact of mitotic index/10 HPF and histological malignancy grade. The results showed a strong association between mitotic figure counts and MIB-1 index (P<0.0001). A correlation was observed between mitotic count per 40 HPF and MIB-1, and between mitotic index per 10 HPF and 40 HPF (P<0.05). Moreover, histological malignancy grade and mitotic figure counts were excellent prognostic factors during three-year follow-up (P<0.05). There was a correlation between the three methods used for the evaluation of cell proliferation and prognostic factors as observed in human breast cancer studies.

Avaliaram-se três métodos de proliferação celular, índice mitótico/10 campos de grande aumento (10 CGA), quatro vezes 10 CGA (40 CGA) e índice de marcação por MIB-1, em uma série de tumores mamários caninos, e as possíveis correlações entre estes métodos. Foram estudados 56 tumores mamários caninos, 23 benignos e 33 malignos. Foi também avaliado o impacto prognóstico do índice mitótico (10 CGA) e o grau histológico maligno em 17 tumores malignos, sete carcinomas ductais e 10 carcinomas metaplásicos. A correlação entre os três métodos para avaliar a proliferação celular e o impacto prognóstico do índice mitótico por 10 CGA e o grau histológico maligno foi realizada. Os resultados mostraram que existe uma forte associação entre contagem de mitose e o índice de marcação por MIB-1(P<0,0001) e correlação entre contagem de mitoses em 40 CGA e índice de marcação por MIB-1 e entre índice mitótico em 10 CGA e 40 CGA (P<0,05). Observou-se correlação entre os três métodos de avaliação da proliferação celular e os fatores prognósticos semelhante aos estudos de câncer de mama humano.

DNA flow cytometry of canine mammary tumors: comparative aspects with human breast tumors

Flow cytometric analysis of DNA content was performed on 28 samples of canine mammary tumors. Nine of them were benign and 19 were malignant. All benign tumors and 11 malignant tumors (57.9 percent) were diploid (P<0.05). Form the aneuploid tumors, five (26.3 percent) were hyperdiploid, one (5.3 percent) hypodiploid, one (5.3 percent) near triploid and one (5.3 percent) multiploid. The analysis of the expression of the markers PR and CD31 revealed a significant difference between diploid and aneuploid tumors (P<0.05). The immunoreactivity of PR was higher in diploid tumors, while the immunoreactivity of CD31 was stronger in aneuploid tumors. No difference between the markers MIB-1, c-erbB2, p53 and Cyclin D1 was observed (P>0.05). Using the flow cytometry analysis and immunohistochemistry, it was found a close relationship between aneuploidy and malignant character of neoplasias, progesterone receptor (PR) negative immunostaining and higher microvases density. No correlation between DNA content and S phase or immunoreactivity for the markers MIB-1, p53, c-erbB2 and Cyclin D1 was observed

Análise por citometria de fluxo de DNA foi realizada em 28 amostras de tumores mamários de cadela. Nove eram benignos e 19 malignos, sendo todos os benignos e 11 malignos (57,9 por cento) diplóides (P<0,05). Dos tumores aneuploides, cinco (26,3 por cento) eram hiperdiploides, um (5,3 por cento) hipodiploide, um (5,3 por cento) triploide e um (5,3 por cento) multiploide. A análise dos marcadores de expressão PR e CD31 revelaram significativa diferença entre tumores diploides e aneuploides (P<0,05). A imunorreatividade do PR foi maior em tumores diplóides e a imunoreatividade do CD 31 maior em tumores aneuploides. Para os marcadores MIB-1, c-erbB-2, p53 e Ciclina D1 não foi observada diferença significativa (P>0,05). Pela citometria de fluxo e pela imunoistoquímica verificaram-se uma relação entre aneuploidia e características malignas das neoplasias, receptor de progesterona imunoreação negativa e alta densidade de microvascular. Não foi observada correlação entre conteúdo de DNA e a fase S ou imunorreatividade para os marcadores MIB-1, c-erbB-2, p53 e Ciclina D1

c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors

The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil) and the Veterinary Faculty of Porto University (Portugal). c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor) in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4 percent) of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001), histological grade (P = 0.0017) and mitotic count (P < 0.05). Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001). These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.

Protocol for the anatomopathological examination of canine mammary tumors

Foi elaborado um protocolo para exame anatomopatológico de tumores de mama em cäes, constituído de três partes: requisiçäo, exame clínico e laudo histopatológico. O exame clínico contém dados sobre a descriçäo macroscópica da lesäo. O laudo histopatológico constituiu-se de campos para descriçäo microscópica pormenorizada das lesöes e classificaçäo da principal lesäo observada. A elaboraçäo do protocolo tem como objetivo estabelecer critérios para estudos e pesquisas sobre neoplasias mamárias em animais e auxiliar no diagnóstico e prognóstico de lesöes mamárias

Pleomorphic lobular carcinoma of the canine mammary gland: histopathologic and immunohistochemical features

This report describes the morphological and immunohistochemical findings of a case of mammary gland pleomorphic lobular carcinoma occurring in the canine species. Histologically, it was characterized by the presence of tumor cells loosely dispersed in the stroma or arranged in a linear pattern showing relatively abundant eosinophilic cytoplasm with an eccentric nuclei. These morphological features, characteristic of pleomorphic mammary gland lobular carcinoma in woman, were not previously described in dogs

Invasive micropapillary carcinoma of the dog mammary gland: a case report

This report describes the morphological and immunohistochemical findings of two cases of breast invasive micropapillary carcinoma occurring in dogs. Histologically, the tumors are characterized by the presence of numerous irregular cystic formations filled out with nests of epithelial cells that exhibit a micropapillary pattern. These morphological features are characteristic of invasive micropapillary carcinoma in woman, a breast tumor not previously described in dogs

A new methodology for the improvement of diagnostic immunohistochemistry in canine veterinary pathology: automated system using human monoclonal and polyclonal antibodies

The autors describe their experience with an automated immunohistochemical system applied to canine tissue samples. Twenty human cellular markers specific monoclonal and polyclonal antibodies and two different antigen retrieval methods were used in normal and neoplastic breast tissue, as well as skin samples obtained from female dogs of pure and mixed breeds. The antibodies tested were the most frequently used in human and veterinary medicine studies, employed with diagnostic purposes in breast pathology, as well as in cancer research. Most of them may be used to study other normal and abnormal tissues and included cytokeratins, progesterone receptor, c-erbB2, p53, MIB-1, PCNA, EMA, vimentin, desmin, alfa-actin, S-100, pan-cadherin, and E-cadherin. The results demonstrated that using an automated staining system it is possible to use different human markers in veterinary pathology. The advantages of automated immunohistochemistry are improved quality, reproducibility, speed, and standardisation

Diagnóstico citológico de tumor mamário metastático canino em derrame pleural / Cytological diagnosis of metastatic canine mammary tumor in pleural effusion

Descreveram-se os achados citomorfológicos de um tumor maligno de mama em uma cadela Poodle de sete anos de idade, o qual foi observado inicialmente pelo exame citológico do derrame pleural. Comparam-se os aspectos citológicos do derrame pleural e punçäo aspirativa com agulha fina do tumor com aqueles descritos para o câncer de mama na espécie humana

Hyperandrogenism due to 3 beta-hydroxysteroid dehydrogenase deficiency with accessory adrenocortical tissue: a hormonal and metabolic evaluation

1. Adrenal ectopic tissue has been detected in the paragonadal region of normal women. In patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, the manifestation of hyperplasia of paragonadal accessory adrenal tissue has been usually reported to occur in males. Probably, this is the first report of a female with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency with ectopic adrenal tissue in ovaries. However, the occurrence of hyperplasia of adrenal rests among women with classical congenital adrenal hyperplasia may not be rare, especially among patients with a late diagnosis. 2. We report a woman with 3 beta-HSD deficiency whose definitive diagnosis was made late at 41 years of age immediately before surgery for the removal of a uterine myoma. During surgery, exploration of the abdominal cavity revealed the presence of bilateral accessory adrenal tissue in the ovaries and in the para-aortic region. The patient had extremely high levels of ACTH (137 pmol/l), DHEA (901.0 nmol/l), DHEA-S (55.9 mumol/l), androstenedione (70.2 nmol/l), testosterone (23.0 nmol/l) and 17 alpha-hydroxypregnenolone (234.4 nmol/l) suggesting 3 beta-HSD deficiency. 3. In view of these elevated androgen levels, with an absolute predominance of DHEA and DHEA-S, we evaluated the effect of this hormonal profile on carbohydrate tolerance and insulin response to glucose ingestion. 4. The patient presented normal glucose tolerance but her insulin response was lower than that of 14 normal women (area under the curve, 3 beta-HSD = 17,680 vs 50,034 pmol/l for the control group over a period of 3 h after glucose ingestion).(ABSTRACT TRUNCATED AT 250 WORDS)

Consideraçöes sobre o câncer localmente avançado de mama (CLAM) acrescidas de identificaçäo dos receptores de estrogênios usando anticorpos monoclonais / Considerations of locally advanced cancer of the breast (LACB) increased of indentification of estrogen receptors by using monoclonal

Para investigar os resultados do tratamento do câncer localmente avançado de mama nós estudamos 49 pacientes, que foram submetidas à associaçäo de telecobaltoterapia convencional e quimioterapia dupla com ciclofosfamida e 5-fluoracil, combinadas com mastectomia radical nos casos operáveis. Obteve-se controle local do tumor em 86,7% dos casos. Näo houve recidivas logorregionais nas pacientes submetidas à cirurgia, índice que alcançou 21,7% nas inoperáveis que receberam só radioterapia e quimioterapia. O seguimento médio das pacientes falecidas foi de 29,5 meses e das sobreviventes, de 79,3 meses. O índice de respostas completas foi de 24,5%. O período médio livre de doença de 22,9 meses e índice global de sobrevida, entre três e cinco anos, de 32,7%. Os receptores de estrogênios foram identificados mediante método imuno-histoquímico (ER-ICA) usando anticorpo monoclonal antiestrogênio (RE, 22-SPy, Abbot). Näo houve diferenças de resultados entre as pacientes RE-positivas e RE-negativas, o que explica pelo adiantado estágio evolutivo dos tumores - no que tange aos índices de respostas completas, período livre de doença e sobrevida global. A presença de receptores de estrogênios correlacionou-se, significativamente, com alguns sinais histopatológicos das neoplasias: grau de diferenciaçäo, quantidade de elastose, ausência de infiltraçäo linfocitária e ausência de necrose

Cytomorphological and immunocytochemical evaluation of fine needle aspirates from high grade non-Hodgkin's lymphomas

Fine needle aspirates from ten patients with high-grade malignant non-Hodgkin's lynmphomas were analyzed by cytomorphology and immunocytochemistry. The following morphologic diagnoses were made: lymphoblastic lymphoma (3 cases), Burkitt's lymphoma (3 cases), mixed small and large cell lymphomas with predominance of large cells (2 cases), and centroblastic lymphoma (2 cases). Immunocytochemistry showed a B-cell phenotype in five cases and a T-cell phenotype in four. One case of lymphoblastic lymphoma was negative for the T and B cell markers used.The results of histological and immunohistochemical analyses performed on surgical biopsies from 8 patients confirmed the morphological diagnosis in all cases. Two cases of Burkitt's lymphoma were submitted only to cytological and immunological diagnosis. The high diagnostic accuracy of combined cytomorphology and immunocytochemical assessmentof fine needle aspirate samples validates the use of the technique in the diagnostic work-up of high-grade non Hodgkin's lymphomas

Utilidade dos metodos imuno-histoquimicos para o diagnostico anatomo-patologico / The usefulness of immunohistochemical methods for the anatomopathologic diagnosis

Com a finalidade de avaliar a contribuicao da imuno-histoquimica ao diagnostico morfologico estudamos 949 casos enviados em consulta ao Laboratorio de Imuno-histoquimica do Departamento de Patologia da Faculdade de Medicina de Botucatu no periodo de 1984 a 1989. Todos os casos foram submetidos as tecnicas de imunoperoxidase pelos metodos do PAP ou ABC. A imuno-histoquimica confirmou o diagnostioco preferencial em 468 casos (49,3 por cento); nao contribuiu em 114 casos (12 por cento) e propos um diagnostico insuspeitado em 49 casos(5,2 por cento). Nos casos em que nao contribuiu, a fixacao inadequada do tecido foi uma das principais responsaveis pela falha da tecnica. A analise destes dados demonstra qua a imuno-histoquimica contribuiu significativamente no diagnostico anatomo-patologico e que deve ser executada por patologista cirurgico treinado e experiente.

A patologia dos especimes de histerectomia em um hospital geral. / The pathology of histerectomy specimens in a general hospital

Os relatorios anatomo-patologicos de 214 especimes de histerectomias realizadas durante o periodo de junho de 1975 a dezembro de 1981, foram revisados. Sangramento vaginal anormal foi a principal indicacao clinica. Leiomiomas estavam presentes em 102 especimes (47,6%), o utero era normal em 15 especimes (6,6%)