Clinical presentation, histological findings, and prognosis in female dogs with mixed mammary neoplasms / Apresentação clínica, achados histológicos e prognóstico em cadelas com neoplasias mamárias mistas

The aim of this study was to describe the clinical and morphological characteristics of mixed mammary neoplasms and verify what characteristics affect the prognosis of female dogs with carcinomas in mixed tumors and carcinosarcomas. This was a retrospective study of 67 female dogs that underwent mastectomies and were diagnosed with benign mixed tumors (n=13), carcinomas in mixed tumors (n=44) and carcinosarcomas (n=10). Data regarding the clinical and histological aspects of the neoplasms were collected and the relation with specific survival times, and hazard ratios (HR) in 24 months was calculated. In univariate analysis, the diagnosis of carcinosarcoma (HR 8.26, p=0.006), carcinomatous areas with micropapillary or solid patterns (HR 17.49; p=0. 001) and lymph node metastasis (HR 7.07;p=0.020) were associated with specific survival. In multivariable analysis, only micropapillary or solid pattern (HR=16.34; p=0.007) remained independent factor associated with lower specific survival. Micropapillary or solid carcinomatous patterns were associated with shorter specific survival time (p=0.002) among animals with carcinomas in mixed tumors. Among the carcinosarcomas, lymph node metastasis (p=0.010) was associated with a shorter specific survival time. In conclusion, carcinomas in mixed tumors and carcinosarcomas vary in prognosis depending on the carcinomatous proliferation patterns and spread of the disease.

O objetivo deste estudo foi descrever as características clínicas e morfológicas das neoplasias mamárias mistas e verificar quais características interferem no prognóstico de cadelas com carcinomas em tumores mistos e carcinossarcomas. Este foi um estudo retrospectivo de 67 cadelas, que foram submetidas a mastectomias e diagnosticadas com tumores mistos benignos (n = 13), carcinomas em tumores mistos (n = 44) e carcinossarcomas (n = 10). Foram coletados dados sobre os aspectos clínicos e histológicos das neoplasias e a relação com o tempo de sobrevida específica e a razão de risco (OR) em 24 meses foram calculadas. Na análise univariada, o diagnóstico de carcinossarcoma (HR 8,26; p=0,006), as áreas carcinomatosas com padrão micropapilar e sólido (HR 17,49; p= 0,001) e metástase linfonodal (HR 7,07; p=0,020) foram associadas à menor sobrevida específica. Na análise multivariável, apenas o padrão micropapilar ou sólido (HR=16,34; p=0,007) permaneceu como fator independente associado à sobrevida. Proliferações carcinomatosas micropapilares ou sólidas (p = 0,002) foram associadas a tempos de sobrevida específica mais curtos entre os animais com carcinomas em tumor misto. Entre os pacientes com carcinossarcoma, metástases em linfonodos (p = 0,010) foram associadas a um menor tempo de sobrevida específica. Em conclusão, os resultados mostraram que os carcinomas em tumores mistos e os carcinossarcomas podem ter prognóstico variável, dependendo do padrão de proliferação carcinomatosa e da disseminação linfática da doença.

Quality of breast reconstruction service at a university hospital as assessed by the patients

Purpose: To evaluate the quality of breast reconstruction service at a university hospital, as assessed by the patients. Methods: This cross-sectional study enrolled adult women who underwent immediate or delayed breast reconstruction by any technique performed at a university hospital between 1 and 24 months before the assessment. The Brazilian version of the Health Service Quality Scale (HSQS) was self-applied to the participants. The HSQS produces percentage scores, which are expressed in values ranging from 0 to 10 for each domain of the scale, and into an overall percentage quality score. The management team was asked to establish a minimum satisfactory score for the breast reconstruction service. Results: Ninety patients were included. The management team considered 8.00 the minimum satisfactory score for the service. The overall percentage score was 93.3%. Only one domain, 'Support,' had an average score lower than that considered satisfactory (7.22 ± 3.0); while the others had higher scores. The domain that scored highest was 'Qualification' (9.94 ± 0.3), followed by 'Result' (9.86 ± 0.4). There was a positive correlation between 'type of oncologic surgery' and 'intentions of loyalty to the service' (ρ = 0.272; p = 0.009) and a negative correlation between 'education' and 'quality of the environment' (ρ = ­0.218; p = 0.039). The higher the patient's level of education, the higher the score attributed to 'relationship' (ρ = 0.261; p = 0.013) and the lower the score of 'aesthetics and functionality' (ρ = ­0.237; p = 0.024). Conclusion: The quality of the breast reconstruction service was considered satisfactory, but there is a demand for structural improvements, better interpersonal relationships, and a stronger support network for patients.

Doxorubicin nephrotoxicity in cats (Felis catus) with malignant mammary neoplasms / Nefrotoxicidade da doxorrubicina em gatas (Felis catus) com neoplasias mamárias malignas

The aim of the study was to investigate the nephrotoxicity of doxorubicin in cats with malignant neoplasms of the mammary gland. All selected cats did not present comorbidities such as nephropathies and/or cardiomyopathies, confirmed by physical and laboratory tests, underwent radical mastectomy associated with regional lymph node excision and were treated with a protocol based on doxorubicin. Renal markers of urea, creatinine, symmetrical dimethylarginine were evaluated during all the treatment, and two months after the end. Abdominal ultrasound, urinalysis and biochemical analysis of protein, urinary creatinine and urinary GGT were performed in the beginning and two months after the end of the treatment, to evaluate possible renal alterations. Six cats did not present renal alterations in any exams performed during the study. Two cats presented azotemia during this study, and one of them stopped the treatment early, because of the intense azotemia. Clinical imaging and laboratory monitoring of patients throughout the treatment is essential, including the measurement of analytes that detect kidney changes early. Thus, it is emphasized that doxorubicin is a safe drug for use in non-nephropathic cats.

O objetivo do estudo foi investigar a nefrotoxicidade da doxorrubicina em gatas com neoplasias malignas da glândula mamária. Todas as gatas selecionadas não apresentaram comorbidades como nefropatias e/ou cardiomiopatias, comprovadas por exames físicos e laboratoriais, foram submetidas à mastectomia radical associada à exérese de linfonodos regionais e tratadas com protocolo baseado em doxorrubicina. Os marcadores renais ureia, creatinina, dimetilarginina simétrica foram avaliados durante todo o tratamento e dois meses após o término. Ultrassonografia abdominal, urinálise e análise bioquímica de proteínas, creatinina urinária e GGT urinária foram realizadas no início e dois meses após o término do tratamento, para avaliar possíveis alterações renais. Seis gatas não apresentaram alterações renais em nenhum dos exames realizados durante o estudo. Duas gatas apresentaram azotemia durante este estudo, e uma delas interrompeu o tratamento precocemente, devido à intensa azotemia. A individualidade de cada paciente deve ser sempre considerada, pois são muitas as variáveis. O monitoramento clínico, com exames complementares, tais como bioquímicos séricos e de imagem dos pacientes durante todo o tratamento, é essencial, especialmente a mensuração de analitos que detectam alterações renais precocemente. Diante disso, ressalta-se que a doxorrubicina é um medicamento seguro para utilização em gatas não nefropatas.

Histone epigenetic modifications and their relationship with cancer: a comparative medicine view / Modificações epigenéticas de histonas e sua relação com o câncer: uma visão da medicina comparada

ABSTRACT: Epigenetic modifications have become highly important in the study of cancer pathogenesis due to research showing that changes in the expression of DNA-associated proteins can affect gene expression but may be reversible after treatment. The changing histones are being studied on a large scale in medicine while recent studies also show this relationship in veterinary medicine. Histone deacetylation is related to tumor progression and overexpression of histone deacetylases (HDACs) is responsible for these changes. The silencing of tumor suppressor genes related to epigenetic changes favors tumor progression; however, using HDAC inhibitors has been shown to effectively reverse these histone changes while having anticancer effects. This research provided an overview of comparative medicine between humans and dogs concerning epigenetic changes while showing the physiological mechanisms and the relationship between cancer and epigenetics, specifically regarding histone acetylation and deacetylation. This overview should contribute to a better understanding of epigenetics and cancer and their relationship with new target-molecular therapies in veterinary medicine and the importance of such studies.

RESUMO: Mudanças epigenéticas assumiram importância na patogênese do câncer a partir de pesquisas que mostraram que mudanças na expressão de proteínas associadas ao DNA podem afetar a expressão gênica e podem ser reversíveis após o tratamento. As alterações nas histonas têm sido estudadas em larga escala na medicina, particularmente no câncer de mama, e estudos recentes mostram essa relação também na medicina veterinária. A desacetilação das histonas está relacionada à progressão tumoral e a superexpressão de histonas desacetilases (HDACs) é responsável por essas alterações. O silenciamento de genes supressores de tumor relacionados a alterações epigenéticas favorece a progressão tumoral, entretanto, o uso de inibidores de HDAC é eficaz em reverter as alterações nas histonas e tem efeitos anticâncer. Uma visão da medicina comparada entre humanos e cães em relação às alterações epigenéticas, será o objetivo deste trabalho, mostrando os mecanismos fisiológicos e a relação entre o câncer e a epigenética, especificamente com a acetilação e desacetilação de histonas. Essa visão contribuirá para um melhor entendimento da epigenética e do câncer, bem como a relação com as novas terapias moleculares-alvo na medicina veterinária e a importância dos estudos neste contexto.

Canine mixed tumors as one of the mammary neoplasia varieties

The most significant interest in veterinary oncology is occupied by tumors of a mixed nature, which are represented by the direct interaction of epithelial and mesenchymal components. According to some data, the formation of cell lineage of mesenchymal cells occurs due to the transformation of epidermal basket cells surrounding the glandular epithelium. In this case, the formation of a cartilage anlage with its further transformation into differentiated bone tissue occurs. The article contains information about the structure and features of the location and interaction of mixed tumors' glandular and stromal components in female dogs (n=29). It was revealed that in addition to simple mixed neoplasms, tumors with proplasia of the mesenchymal component into highly differentiated cartilage or bone tissue were also often registered. To confirm subcellular changes in the expression of certain types of proteins, such as a-SMA and vimentin, an IHC study was used. The expression of the studied biomarkers was established in mesenchymal fibroblastic differon cells and myoepithelial cells. The intensity of immunoreactive material expression ranged from moderate (2+) to strong (3+), indicating changes in myoepithelial cells' genotype during the formation of mixed mammary neoplasms.(AU)

Efficacy of fine needle aspiration in the diagnosis of spontaneous mammary tumors / Eficácia da citologia aspirativa no diagnóstico de tumores mamários espôntaneos / La eficacia de la aspiración con aguja fina en el diagnóstico de tumores mamarios espontáneos

The cytopathology exam has been utilized to diagnose mammary disorders in female dogs. The success of cytopathology results depends on, among other factors, the diagnostic accuracy of the exam. The present study aimed to compare the cytopathological and histopathological findings from mammary disorder cases in female dogs and evaluate the lesion cytopathology exam accuracy. The concordance degree was evaluated between the cytopathology and histopathology exams of 67 female dogs, carriers of palpable breast lumps, cared for at the university hospital from which the following indicators were calculated: sensitivity, specificity, positive predictive value, negative predictive value, false positives, false negatives, and exam accuracy. The sensitivity was 95.23%, the specificity 75%, positive predictive value 98.36%, negative predictive value 60%, and accuracy 94.02%. There were 2 false negatives and 1 false positive. In conclusion the cytopathology exam can be amply utilized as a means of diagnosis with high accuracy and sensitivity in the first examination of female dogs with mammary tumors.(AU)

O exame citológico tem sido utilizado no diagnóstico das afecções mamárias das cadelas. O êxito no resultado da citologia dependerá, além de outros fatores, da acurácia diagnóstica deste exame. O objetivo deste estudo foi comparar os achados citológicos e histológicos das afecções mamárias de cadelas e avaliar a acurácia do exame citológico nestas lesões. Avaliou-se o grau de concordância entre os exames citológico e histológico de 67 cadelas, portadoras de nódulo mamário palpável, atendidas em um hospital universitário e foram calculados os indicadores: sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo, falso positivo, falso negativo e acurácia do exame. A sensibilidade foi de 95,23%, a especificidade de 75%, o valor preditivo positivo de 98,36%, o valor preditivo negativo de 60% e a acurácia de 94,02%. Ocorreu 1 resultado falso positivo e 2 falso negativos. Conclui-se que o exame citológico pode ser amplamente utilizado como meio de diagnóstico com elevada acurácia e sensibilidade no atendimento primário das cadelas com tumor de mama.(AU)

El examen citológico se ha usado en el diagnóstico de cáncer de mama en perras. El éxito de la citología depende, entre otros factores, la precisión diagnóstica de este examen. El objetivo de este estudio fue comparar los resultados de citología y examen histológico de las enfermedades de mama en las perras y evaluar la exactitud de la citología de estas lesiones. Se evaluó el grado de acuerdo entre los exámenes citológicos e histológicos de 67 perros, que sufren de bulto palpable en la mama atendidos en un hospital universitario y se calcularon los indicadores: sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo, falsos positivos, falsos negativo y exactitud de la prueba. La sensibilidad fue del 95,23%, especificidad 75%, valor predictivo positivo del 98,36%, valor predictivo negativo del 60% y el 94,02% de precisión. Hubo un resultado positivo falso y dos falsos negativos. Se concluye que el examen citológico puede ser ampliamente utilizado como una herramienta de diagnóstico de alta precisión y sensibilidad en la atención primaria de perros con cáncer de mama. (AU)

Hiperplasia fibroepitelial mamária em um gato macho: relato de caso / Mammary fibroepithelial hyperplasia in a male cat: case report

As neoplasias mamárias representam a terceira neoplasia mais comum em gatas, enquanto nos machos a incidência é rara. Esse trabalho relata o caso de um gato macho, não castrado, atendido no Hospital Veterinário da Universidade Estadual do Ceará, com uma neoformação mamária. O diagnóstico inicial, obtido por meio de punção aspirativa por agulha fina, sugeriu a presença de carcinoma mamário. Exames de imagem como a radiografia torácica e a ultrassonografia abdominal não evidenciaram a presença de metástase no parênquima pulmonar e nos órgãos abdominais, respectivamente. O tratamento instituído foi a remoção cirúrgica da neoformação, pela técnica de mastectomia parcial bilateral. O exame histopatológico da massa evidenciou uma hiperplasia fibroepitelial. Diante disso, conclui-se que, apesar de raras, as neoformações mamárias em gatos do sexo masculino podem ocorrer, devendo, dessa forma, compor parte da lista de diagnósticos diferenciais para aumentos de volume na região ventral desses animais.(AU)

Mammary neoplasms represent the third most common neoplasm in queens, while in tomcats the incidence is rare. This study reports the case of a tomcat, not neutered, treated at the Veterinary Hospital of the State University of Ceará, with a mammary neoformation. The initial diagnosis, obtained through aspiration cytology, suggested the presence of mammary carcinoma. Imaging tests such as thoracic radiography and abdominal ultrasound, did not show the presence of metastasis in the lung parenchyma and abdominal organs, respectively. The chosen treatment was the surgical removal of the neoformation, using the bilateral partial mastectomy technique. Histopathological examination of the mass showed a mammary fibroepithelial hyperplasia. Therefore, it is concluded that, although rare, mammary neoformations in male cats can occur, thus, it should be part of the list of differential diagnoses for increases in volume in the ventral region of these animals.(AU)

Spectral analysis, in vitro cytotoxicity and antibacterial studies of bioactive principles from the leaves of Conocarpus lancifolius, a common tree of Jazan, Saudi Arabia

Abstract The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo-N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2':4',2-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-1 representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram-negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.

Resumo O objetivo do presente estudo foi analisar os compostos bioativos das folhas de Conocarpus lancifolius (C. lancifolius). A análise por GC-MS do extrato metanólico quente das folhas (HMEL) de C. lancifolius exibiu os compostos bioativos como 1- (3-Metoxi-2-nitrobenzil) isoquinolina, morfina-4-ol-6,7- diona, 1-bromo-N-metil-, fitol, ácido hexadecanoico, 2,3-di-hidroxipropil éster, 2,2 ': 4', 2 - tertiofeno, isoalocolato de etil, óxido de cariofileno, campesterol, epiglobulol, colestano -3-ol, 2-metileno-, (3á, 5à) -, dasycarpidan-1-metanol, acetato (éster) e ácido oleico, éster eicosílico. A análise FT-IR de HMEL de C. lancifolius mostrou um pico único em 3184, 2413, 1657 cm-1 representando ácido cumarico, ácido clorogênico e ácido ferúlico. O HMEL de C. lancifolius inibiu ativamente a proliferação de células de câncer de mama MCF-7 ATCC na concentração de 72,66 ± 8,21 µg / ml como valor de IC50. O HMEL de C. lancifolius também revelou bom espectro de atividade contra culturas de bactérias Gram-positivas e Gram-negativas rastreadas neste trabalho. A atividade observada mostrou efeitos mais ou menos semelhantes contra bactérias rastreadas. No entanto, a magnitude da potencialidade foi significativamente menor em comparação com o disco de ciprofloxacina padrão em nível de p 0,001 (intervalos de confiança de 99%). Além disso, o estudo demonstrando os compostos bioativos pode ser isolado das folhas de C. lancifolius.

Diagnostic applicability of infrared thermography in the evaluation of canine mammary tumors / Aplicabilidade diagnóstica da termografia infravermelha na avaliação dos tumores mamários caninos

Mammary tumors have a high prevalence in bitches and women, and are related to high rates of morbidity and mortality. For the human species, thermography has stood out as a diagnostic tool for breast cancer. However, its clinical benefit in bitches remains unknown. Thus, the goal of the present study was to evaluate the diagnostic applicability of infrared thermography for canine mammary tumors, as well as to correlate tumor temperature with mitotic index and tumor volume. Thermographic and digital images of eight bitches with mammary neoplasms were captured. Thermograms were entered into the FLIR tools software and the temperature of 15 tumor and 15 healthy glands from the contralateral mammary chain was analyzed. There was no significant difference (p = 0.786) between the mean temperature of neoplastic (33.71°C ± 1.86) and healthy (33.54°C ± 1.59) glands. There was a negative and moderate correlation between tumor temperature and mitotic index (ρ = -0.52 p = 0.049). However, no correlation was detected between mammary temperature and tumor volume (p = 0.10). Although thermography allowed no distinction between neoplastic and healthy mammary glands in bitches, it may be promising to assess the proliferative rate of tumors. In addition, malignant neoplasms may be more often hypothermic than healthy tissue.(AU)

Os tumores mamários apresentam alta prevalência em cadelas e mulheres, sendo relacionados a elevadas taxas de morbidade e mortalidade. Para a espécie humana, a termografia tem se destacado como ferramenta diagnóstica do câncer de mama. Entretanto, o seu benefício clínico em cadelas permanece desconhecido. Assim, o objetivo do presente estudo foi ava-liar a aplicabilidade diagnóstica da termografia infravermelha para os tumores mamários caninos, bem como correlacionar a temperatura tumoral com o índice mitótico e volume tumoral. Foram capturadas imagens termográficas e digitais de oito cadelas com neoplasias mamárias. Os termogramas foram inseridos no software FLIR tools e analisou-se a temperatura de 15 mamas tumorais e 15 hígidas da cadeia mamária contralateral. Não houve diferença significativa (p = 0,786) entre a tempera-tura média das glândulas neoplásicas (33,71°C ± 1,86) e saudáveis (33,54°C ± 1,59). Houve correlação negativa e moderada entre a temperatura tumoral e índice mitótico (ρ = -0,52 p = 0,049). Entretanto, não foi observada correlação entre tempe-ratura e volume tumoral (p = 0,10). Apesar da termografia não ter permitido a diferenciação das mamas neoplásicas e saudá-veis de cadelas, ela pode ser uma forma promissora para avaliação da taxa proliferativa dos tumores. Além disso, as neoplasias malignas podem apresentar-se mais frequentemente hipotérmicas em relação ao tecido saudável.(AU)

CA 15-3, CRP, and LDH correlates with prognostic parameters in canine mammary neoplasms

The identification of putative prognostic factors in canine mammary neoplasms (CMNs) has been focused on tissue-specific biomarkers, but the serum biomarkers, including cancer antigen 15-3 (CA 15-3), c-reactive protein (CRP), and lactate dehydrogenase (LDH) have been demonstrated to display clinical application in cases of CMNs. The aim of the study was to evaluate the levels of these serum biomarkers and their association with well-established prognostic factors in CMNs. Samples from 15 female canines with CMNs and 15 clinically healthy ones were collected. The results were evaluated using the Tukey's, Pearson, or Spearman tests. The cut-off point, sensitivity, specificity, and area under curve (AUC) were evaluated using the receiver operating characteristic (ROC) curve analysis in a logistic regression model (P<0.05). The levels of CA 15-3, CRP and LDH were significantly higher in the serum of female dogs with CMNs compared to the healthy ones. Moreover, these factors were positively correlated with ulceration, tumor size, histopathological grade, metastatic lymph node, and clinical staging. Female dogs with CMNs were found to exhibit highest serum levels of CA 15-3, CRP, and LDH. Therefore, they can be applied to improve the efficacy of the diagnosis and prognostic evaluation in casas of CMNs.(AU)

B-mode and Doppler ultrasound of bitches' kidneys with mammary neoplasia submitted to adjuvant chemotherapy / Ultrassonografia modo-B e Doppler dos rins de cadelas com neoplasias mamárias submetidas à quimioterapia adjuvante

Mammary neoplasia represents the most frequently diagnosed type of neoplasia in bitches. Although surgical removal is the procedure of choice for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have occurred in the field of cancer therapy, the systemic repercussions of these drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and preventive monitoring of patients represent important strategies to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in abdominal cavity organs. Acting complementary to the B-mode evaluation, Doppler mapping proves to be efficient in recognizing alterations in vascular hemodynamics. Therefore, the objective of the present study was to evaluate the use of B-mode and Doppler ultrasound to identify renal morphological and hemodynamic alterations in bitches with mammary neoplasia submitted to adjuvant chemotherapy protocols that associate gemcitabine with carboplatin. Thirteen bitches were included, without distinction of breed and between seven and 13 years of age. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after each cycle (T1), for 42 days. No morphological changes were observed in B-mode throughout the chemotherapy protocol. However, the Doppler velocimetry indices demonstrated statistical differences before (T0) and after (T1) the administration of the drugs. It was concluded that Doppler ultrasound could be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs and potentially causing renal injury.

As neoplasias mamárias representam o tipo de neoplasma mais frequentemente diagnosticado em fêmeas da espécie canina. Embora a remoção cirúrgica seja o procedimento de eleição para a conduta terapêutica, os protocolos quimioterápicos aparecem como importantes aliados e adjuvantes. Apesar dos grandes avanços ocorridos na área da terapia oncológica, as repercussões sistêmicas destes fármacos ainda impõem importantes limitações ao seu uso. Neste sentido, o desenvolvimento de protocolos terapêuticos cada vez mais direcionados e o monitoramento preventivo dos pacientes representam estratégias importantes para evitar possíveis complicações - dentre elas, a injúria renal aguda (IRA). Rotineiramente, a avaliação ultrassonográfica é utilizada para identificação de variações morfológicas ou metastáticas em órgãos da cavidade abdominal. Atuando de forma complementar à avaliação em modo-B, o mapeamento Doppler mostra-se eficiente no reconhecimento de alterações na hemodinâmica vascular. Portanto, o objetivo do presente estudo foi avaliar a utilização da ultrassonografia modo-B e Doppler como método para identificação de alterações morfológicas e hemodinâmicas renais em cadelas com neoplasias mamárias submetidas a protocolos quimioterápicos adjuvantes que associam a gencitabina à carboplatina. Foram incluídas 13 fêmeas caninas, sem distinção quanto a raça e com idades entre sete e 13 anos. Os animais foram avaliados ultrassonograficamente em dois momentos distintos durante três ciclos quimioterápicos consecutivos: antes (T0) e uma hora e meia após a realização de cada ciclo (T1), totalizando 42 dias. Não foram observadas alterações morfológicas em modo-B ao longo do protocolo quimioterápico. Entretanto, os índices dopplervelocimétricos demonstraram diferenças estatísticas antes (T0) e após (T1) a administração dos fármacos. Concluiu-se que a ultrassonografia Doppler pode ser utilizada como método complementar para o monitoramento da resposta renal de pacientes expostos a fármacos nefrotóxicos e potencialmente causadores de injúrias renais.

Spectral analysis, in vitro cytotoxicity and antibacterial studies of bioactive principles from the leaves of Conocarpus lancifolius, a common tree of Jazan, Saudi Arabia / Análise espectral, citotoxicidade in vitro e estudos antibacterianos de princípios bioativos das folhas de Conocarpus lancifolius, uma árvore comum de Jazan, Arábia Saudita

Abstract The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo-N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2':4',2"-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-1 representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram-negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.

Resumo O objetivo do presente estudo foi analisar os compostos bioativos das folhas de Conocarpus lancifolius (C. lancifolius). A análise por GC-MS do extrato metanólico quente das folhas (HMEL) de C. lancifolius exibiu os compostos bioativos como 1- (3-Metoxi-2-nitrobenzil) isoquinolina, morfina-4-ol-6,7- diona, 1-bromo-N-metil-, fitol, ácido hexadecanoico, 2,3-di-hidroxipropil éster, 2,2 ': 4', 2 " - tertiofeno, isoalocolato de etil, óxido de cariofileno, campesterol, epiglobulol, colestano -3-ol, 2-metileno-, (3á, 5à) -, dasycarpidan-1-metanol, acetato (éster) e ácido oleico, éster eicosílico. A análise FT-IR de HMEL de C. lancifolius mostrou um pico único em 3184, 2413, 1657 cm-1 representando ácido cumarico, ácido clorogênico e ácido ferúlico. O HMEL de C. lancifolius inibiu ativamente a proliferação de células de câncer de mama MCF-7 ATCC na concentração de 72,66 ± 8,21 µg / ml como valor de IC50. O HMEL de C. lancifolius também revelou bom espectro de atividade contra culturas de bactérias Gram-positivas e Gram-negativas rastreadas neste trabalho. A atividade observada mostrou efeitos mais ou menos semelhantes contra bactérias rastreadas. No entanto, a magnitude da potencialidade foi significativamente menor em comparação com o disco de ciprofloxacina padrão em nível de p < 0,001 (intervalos de confiança de 99%). Além disso, o estudo demonstrando os compostos bioativos pode ser isolado das folhas de C. lancifolius.

Spectral analysis, in vitro cytotoxicity and antibacterial studies of bioactive principles from the leaves of Conocarpus lancifolius, a common tree of Jazan, Saudi Arabia / Análise espectral, citotoxicidade in vitro e estudos antibacterianos de princípios bioativos das folhas de Conocarpus lancifolius, uma árvore comum de Jazan, Arábia Saudita

The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2’:4’,2”-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-¹ representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.

O objetivo do presente estudo foi analisar os compostos bioativos das folhas de Conocarpus lancifolius (C. lancifolius). A análise por GC-MS do extrato metanólico quente das folhas (HMEL) de C. lancifolius exibiu os compostos bioativos como 1- (3-Metoxi-2-nitrobenzil) isoquinolina, morfina-4-ol-6,7- diona, 1-bromo-N-metil-, fitol, ácido hexadecanoico, 2,3-di-hidroxipropil éster, 2,2 ‘: 4’, 2 ” - tertiofeno, isoalocolato de etil, óxido de cariofileno, campesterol, epiglobulol, colestano -3-ol, 2-metileno-, (3á, 5à) -, dasycarpidan-1-metanol, acetato (éster) e ácido oleico, éster eicosílico. A análise FT-IR de HMEL de C. lancifolius mostrou um pico único em 3184, 2413, 1657 cm-¹ representando ácido cumarico, ácido clorogênico e ácido ferúlico. O HMEL de C. lancifolius inibiu ativamente a proliferação de células de câncer de mama MCF-7 ATCC na concentração de 72,66 ± 8,21 µg/ml como valor de IC50. O HMEL de C. lancifolius também revelou bom espectro de atividade contra culturas de bactérias Gram-positivas e Gram-negativas rastreadas neste trabalho. A atividade observada mostrou efeitos mais ou menos semelhantes contra bactérias rastreadas. No entanto, a magnitude da potencialidade foi significativamente menor em comparação com o disco de ciprofloxacina padrão em nível de p < 0,001 (intervalos de confiança de 99%). Além disso, o estudo demonstrando os compostos bioativos pode ser isolado das folhas de C. lancifolius.

Spectral analysis, in vitro cytotoxicity and antibacterial studies of bioactive principles from the leaves of Conocarpus lancifolius, a common tree of Jazan, Saudi Arabia / Análise espectral, citotoxicidade in vitro e estudos antibacterianos de princípios bioativos das folhas de Conocarpus lancifolius, uma árvore comum de Jazan, Arábia Saudita

The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2:4,2”-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-¹ representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.(AU)

O objetivo do presente estudo foi analisar os compostos bioativos das folhas de Conocarpus lancifolius (C. lancifolius). A análise por GC-MS do extrato metanólico quente das folhas (HMEL) de C. lancifolius exibiu os compostos bioativos como 1- (3-Metoxi-2-nitrobenzil) isoquinolina, morfina-4-ol-6,7- diona, 1-bromo-N-metil-, fitol, ácido hexadecanoico, 2,3-di-hidroxipropil éster, 2,2 ‘: 4, 2 ” - tertiofeno, isoalocolato de etil, óxido de cariofileno, campesterol, epiglobulol, colestano -3-ol, 2-metileno-, (3á, 5à) -, dasycarpidan-1-metanol, acetato (éster) e ácido oleico, éster eicosílico. A análise FT-IR de HMEL de C. lancifolius mostrou um pico único em 3184, 2413, 1657 cm-¹ representando ácido cumarico, ácido clorogênico e ácido ferúlico. O HMEL de C. lancifolius inibiu ativamente a proliferação de células de câncer de mama MCF-7 ATCC na concentração de 72,66 ± 8,21 µg/ml como valor de IC50. O HMEL de C. lancifolius também revelou bom espectro de atividade contra culturas de bactérias Gram-positivas e Gram-negativas rastreadas neste trabalho. A atividade observada mostrou efeitos mais ou menos semelhantes contra bactérias rastreadas. No entanto, a magnitude da potencialidade foi significativamente menor em comparação com o disco de ciprofloxacina padrão em nível de p < 0,001 (intervalos de confiança de 99%). Além disso, o estudo demonstrando os compostos bioativos pode ser isolado das folhas de C. lancifolius.(AU)

Hematological and biochemical alterations in female dogs with mammary cancer and inflammatory carcinoma / Alterações hematológicas e bioquímicas em cadelas com neoplasias mamárias e carcinoma inflamatório

Hematological and biochemical alterations in animals with neoplasms may result from the direct effects of tumor growth or paraneoplastic syndromes. The objective of this study was to evaluate these hematological and biochemical alterations in female dogs with mammary tumors and with inflammatory carcinoma (IC). Blood samples were collected from 43 female dogs divided into three groups according to clinical staging: Group 1 (G1) - animals in initial stage (T1,2,3N0M0, N=17), Group 2 (G2) - animals in advanced stage (T1,2,3N1M0,1, N=15) and Group 3 (G3) - animals presenting IC (N=11). Hematological and biochemical parameters obtained were related to patients' clinical staging. Among alterations, the most common were anemia, neutrophilic leukocytosis, monocytosis, increased ALT, AST, and hypoalbuminemia, mainly in dogs in advanced clinical staging and with inflammatory carcinoma.

Aterações hematológicas e bioquímicas em animais portadores de neoplasias podem resultar dos efeitos diretos do crescimento tumoral ou de síndromes paraneoplásicas. O objetivo deste estudo foi avaliar as alterações hematológicas e bioquímicas em cadelas com neoplasias mamárias e carcinoma inflamatório (IC). Foram coletadas amostras de sangue de 43 cadelas divididas em três grupos de acordo com o estadiamento clínico: grupo 1 (G1) - cadelas em estádio inicial (T1,2,3N0M0, N=17), grupo 2 (G2) - cadelas em estádio avançado (T1,2,3N1M0,1, N=15) e grupo 3 (G3) - cadelas que apresentaram IC (N=11). Os parâmetros hematológicos e bioquímicos obtidos foram relacionados com o estadiamento clínico das pacientes. Entre as alterações, as mais comuns foram anemia, leucocitose neutrofílica, monocitose, aumento de ALT, AST e hipoalbuminemia, principalmente em cadelas em estadiamento clínico avançado e com carcinoma inflamatório.

Association between vitamin D and malignant mammary tumors in obese female dogs

Overweight and obesity are known risk factors that are involved in the development and aggressiveness of breast tumors in women. In situations of obesity, local and systemic inflammation may worsen the prognosis of oncological patients. Moreover, hypovitaminosis D increases the risk of breast tumors in women. In female dogs, low vitamin D levels have been found in cases of lymphoma, osteosarcoma and mast cell tumor. The present study aimed to make correlations between body fat composition and serum 25(OH)D concentration in female dogs with mammary tumors. Two experimental groups were formed: healthy female dogs (n = 12; control group) and female dogs with mammary tumors (n = 11). An analysis on body composition was performed using dual-energy X-ray absorptiometry (DXA) equipment. In the tumor group, multicentric nodules were most prevalent (63,6%), with diameters of up to 8.2 cm. The most frequent histopathological diagnosis was tubular carcinoma (45.5%), and 9.1% presented metastases in axillary lymph nodes. The mean 25(OH)D concentration in the female dogs with mammary tumors (37.6 ng mL-1) was lower than the level in the control group (65.4 ng mL-1). Multivariate statistical analysis showed that elderly female dogs with malignant mammary tumors and high body fat levels presented lower 25(OH)D concentrations than those of the control group. It was concluded that female dogs with higher body adiposity presented mammary tumors of higher aggressivity, and that the higher the fat percentage was in the female dogs with malignant mammary tumors, the lower their vitamin D concentration was.(AU)

Phytochemical and biological attributes of Bauhinia variegata L. (Caesalpiniaceae) / Atributos fitoquímicos e biológicos de Bauhinia variegata L. (Caesalpiniaceae)

Bauhinia variegata plant is a very popular and traditionally potent ethnomedicine. Therefore, it is need of hour to study ameliorative characteristics of B. variegata for novel secondary metabolites. The current study was designed to explore antiproliferative potential of B. variegata due to scant reports on this aspect. Extracts of various parts (flowers, leaves, bark, stem, and roots) were prepared by successive maceration using organic solvents in increasing order of polarity (n-hexane, ethyl acetate, methanol, and water). The determination of polyphenolic contents was done by using colorimetric methods while antioxidant potential was measured using reducing power assay. Brine shrimp lethality assay was performed for determining preliminary cytotoxicity and antiproliferative activity against breast cancer MCF-7 cell line using MTT protocols. Moreover, antimicrobial activities were detected by using disc diffusion assay. The alpha-amylase assay was performed to monitor the antidiabetic potential of the plant. In case of phytochemical analysis methanolic extract of leaves and bark showed highest phenolic and flavonoids contents. n-Hexane and ethyl acetate extracts of stem and roots exhibited more than 90% mortality with LD50 ranges between 1-25 µg/mL when studied by brine shrimp lethality assay. n-Hexane and ethyl acetate extracts of roots and stem also showed antiproliferative activity against human breast cancer MCF-7 cell line with IC50 values ranges between 12.10-14.20 µg/mL. Most of the extracts displayed moderately high antibacterial and antifungal activities. The n-hexane extract of roots showed antidiabetic activity with 60.80 ± 0.20% inhibition of alpha-amylase. In sum, these preliminary results will be useful for further compound isolation from selected plant parts for the discovery of antibacterial, antidiabetic, and anticancer lead candidates.

A planta Bauhinia variegata é uma etnomedicina muito popular e tradicionalmente potente. Portanto, as características de melhoria de B. variegata foram estudadas. Foi avaliada a determinação dos teores antioxidantes e polifenólicos. O ensaio de letalidade do camarão de salmoura foi realizado para determinar a citotoxicidade preliminar e a atividade antiproliferativa contra linhas de células de câncer de mama MCF-7 usando protocolos de MTT. Além disso, foram detectadas atividades antimicrobianas. O ensaio da alfa-amilase foi realizado para monitorar o potencial antidiabético da planta. Dentre vinte amostras diferentes, o extrato metanólico (EM) da casca apresentou os maiores teores fenólicos totais. A EM das folhas apresentou excelente conteúdo de flavonoides, atividade antioxidante significativa foi exibida pelo extrato hexânico do caule. O extrato do caule de hexano exibe 77,40% como citotóxico em DL50 10,50 µg/mL quando avaliado através do ensaio de letalidade de artêmia. Extratos de hexano e acetato de etila de raiz e caule mostraram atividade antiproliferativa contra a linhagem celular MCF7 de câncer de mama humano (IC50 12,10-14,20 µg/mL). Para potencial antimicrobiano importante, vários extratos exibiram excelentes atividades antibacteriana e antifúngica, enquanto o extrato de n-hexano da raiz mostrou atividade antidiabética (60,80 ± 0,20% na concentração de 200 µg/mL). Em suma, estes resultados preliminares serão úteis para isolamento adicional de compostos a partir de partes de plantas selecionadas para a descoberta de candidatos a antibacterianos, antidiabéticos e anticâncer.

Canine mammary neoplasms - evaluation of tumor microenvironment

Background: The tumor microenvironment is an important target of studies in different types of neoplasms. Understanding the role of general components such as immune, vascular and fibroblastic cells has the objective of contributing to prognosis and treatment. The aim of this study was to evaluate the relationship between mast cells and angiogenesis in benign and malignant mammary neoplasms by investigating the role of degranulation and microlocation of mast cells and neoformed vessels in canine mammary neoplasms. Materials, Methods & Results: Mammary glands (n = 122) from 50 female dogs submitted to mastectomy without chemotherapy were evaluated and categorized into 3 groups: control group (n = 46); malignant group (n = 57) and benign group (n = 19). Lymph nodes without changes (n = 59) and with metastases (n = 6) were also evaluated. To evaluate the MCD (mast cell density) and angiogenesis, Toluidine Blue (0.1%) and Gomori’s Trichrome techniques were performed and adapted from previous studies. Photomicrographs of 10 hotspot areas on a 40x objective lens of the mammary glands and lymph nodes were captured to assess MCD and angiogenesis. In the absence of these areas, random fields were captured. For the mammary glands of the malignant and benign groups, 20 fields were analyzed, as the analysis considered the microlocation (peritumoral and intratumoral). Counting was performed manually using ImageJ software version 1.42q by 2 observers. The statistical analysis were performed using SPSS software version 19.0. The most frequent histological type in the malignant group was carcinoma in mixed tumor (68.42%; 39/57) and in the benign group was benign mixed tumor (57.89%; 11/19). Female dogs without breed pattern were more frequently affected represented 70% of the animals and the mean age was 9 years and 8 months ± 3 years and 1 month...

Canine mammary neoplasms - evaluation of tumor microenvironment

Background: The tumor microenvironment is an important target of studies in different types of neoplasms. Understanding the role of general components such as immune, vascular and fibroblastic cells has the objective of contributing to prognosis and treatment. The aim of this study was to evaluate the relationship between mast cells and angiogenesis in benign and malignant mammary neoplasms by investigating the role of degranulation and microlocation of mast cells and neoformed vessels in canine mammary neoplasms. Materials, Methods & Results: Mammary glands (n = 122) from 50 female dogs submitted to mastectomy without chemotherapy were evaluated and categorized into 3 groups: control group (n = 46); malignant group (n = 57) and benign group (n = 19). Lymph nodes without changes (n = 59) and with metastases (n = 6) were also evaluated. To evaluate the MCD (mast cell density) and angiogenesis, Toluidine Blue (0.1%) and Gomoris Trichrome techniques were performed and adapted from previous studies. Photomicrographs of 10 hotspot areas on a 40x objective lens of the mammary glands and lymph nodes were captured to assess MCD and angiogenesis. In the absence of these areas, random fields were captured. For the mammary glands of the malignant and benign groups, 20 fields were analyzed, as the analysis considered the microlocation (peritumoral and intratumoral). Counting was performed manually using ImageJ software version 1.42q by 2 observers. The statistical analysis were performed using SPSS software version 19.0. The most frequent histological type in the malignant group was carcinoma in mixed tumor (68.42%; 39/57) and in the benign group was benign mixed tumor (57.89%; 11/19). Female dogs without breed pattern were more frequently affected represented 70% of the animals and the mean age was 9 years and 8 months ± 3 years and 1 month...(AU)

The prognostic significance of immunophenotypes in canine malignant mammary tumors / [Significância prognóstica dos imunofenótipos em tumores mamários malignos caninos]

Canine malignant mammary neoplasms (CMMN) exhibit behavioral variability with the patient survival time depending on several prognostic factors. In the present study, 134 CMMN were selected and different immunophenotypes and their associations with clinical and pathological parameters were identified. The tumors were classified as follows: 46% of luminal B HER2-, 34% of luminal A, 13% of triple-negative, and 7% of luminal B HER2+. Shorter specific survival time were associated with larger tumor sizes (>3.0 cm, HR=1.94; P=0.0209), lymph node metastasis or distant metastasis (HR= 2.82; P <.0001), more aggressive histological types (HR= 7.15, P<0.0001), higher histological grades (HR= 12.97 P=0.011), angiolymphatic invasion (HR=4.68, P<0.0001) and luminal B HER2 - (HR= 3.27, P<0.0001) and luminal B HER2 + (HR= 7.14 P<0.0001) immunophenotypes. In patients with lymph nodal metastasis, shorter survival times were associated with luminal immunophenotype B HER2 + (P=0.003). However, in patients without metastasis, an increased risk of death was associated with the aggressive histological type. In conclusion, the classification in our study allowed us to identify subtypes with different prognoses in canine malignant mammary tumors. Factors such as clinical stage, histological type, luminal B HER2+ subtype, and angiolymphatic invasion were the most important prognostic factors.

Neoplasias mamárias malignas caninas (CMMN) apresentam variável comportamento biológico e o tempo de sobrevida depende de diversos fatores prognósticos. Neste estudo, foram selecionadas 134 CMMN, bem como identificados diferentes imunofenótipos e suas associações com parâmetros clínicos e patológicos. Os tumores foram classificados em: 46% luminal B HER2-, 34% luminal A, 13% triplo negativo e 7% luminal B HER2+. Menores taxas de sobrevida específica foram associadas a tamanhos de tumor maiores (> 3,0cm; HR = 1,94; P = 0,0209), metástases em nodais ou a distância (HR = 2,82; P <0,0001), tipos histológicos mais agressivos (HR = 7,15; P <0,0001), graus histológicos mais elevados (HR = 12,97; P = 0,011), invasão angiolinfática (HR = 4,68; P <0,0001) e aos imunofenótipos luminal B HER2- (HR = 3,27; P <0,0001) e luminal B HER2+ ( HR = 7,14; P <0,0001). Em pacientes com estágio avançado, menor sobrevida específica foi associada ao imunofenótipo luminal B HER2+ (P = 0,003). Entretanto, em estágio inicial, um risco aumentado de óbito foi associado a tipos histológicos agressivos. Em conclusão, a classificação utilizada no presente estudo permitiu identificar subtipos com diferentes prognósticos em CMMN. Estágio clínico, tipo histológico, subtipo luminal B HER2+ e invasão angiolinfática foram os fatores prognósticos mais importantes.