GATA-3 expression and its correlation with prognostic factors and survival in canine mammary tumors.

Introduction: The transcription factor GATA-3 plays a significant role in mammary gland development and differentiation. Recent studies on human oncology have demonstrated its association with favorable pathologic factors in breast cancer. Canine mammary tumours, proposed as comparative and translational study models, have epidemiological, clinical, biological, and genetic characteristics similar to those of human breast cancers. Methods: Here, we evaluated the frequency of GATA-3 expression in mammary tumors of dogs and its relationship with prognostic factors and survival. Tumor samples were obtained from 40 female dogs and grouped according to histological type into benign tumors (n = 10), carcinoma in mixed tumors (CMTs) (n = 20), and aggressive tumors (n = 10). CMTs were further separated according to histological grade, and data on clinical staging and diagnosis, histopathological grading, and survival rate were collected. Results: GATA-3 and estrogen receptor (ER) expression were higher in benign and well-differentiated carcinomas than in aggressive tumors, which showed greater Ki-67 expression. The expression rate of ER in the studied groups was equivalent to that of GATA-3. We identified a strong positive correlation between GATA-3 and ER expression frequencies and a negative correlation between those of GATA-3 and Ki-67. There were associations between GATA-3 (p < 0.001), Ki-67 (p = 0.003), tumor size (p < 0.001), clinical stage (p = 0.002), lymph node metastasis (p < 0.001), and histological grade (p < 0.001) by univariate survival analysis. The parameters ER (p = 0.015) and GATA-3 (p = 0.005) also influenced survival in a multifactorial manner. Discussion: Kaplan-Meier analysis of survival curves validated our previous findings that dogs with GATA-3 expression in ≥79.4% of cells had significantly higher survival rates (p < 0.001). The performance analysis showed that the expression of GATA-3 in ≥79.4% of cells effectively predicted survival or death in dogs with mammary tumors. Collectively, these results suggest that GATA-3 can be a relevant marker in the study of mammary tumor progression and has potential as a prognosis marker for predicting outcomes in canine mammary tumors.

Biofilm formation in vitro by Leptospira interrogans strains isolated from naturally infected dogs and their role in antimicrobial resistance.

Leptospira interrogans is a biofilm-forming pathogen, however, there are few data involving Brazilian strains isolated from dogs and their antimicrobial sensitivity in planktonic and biofilm forms. The potential for biofilm formation and antimicrobial resistance in naturally infected dogs is a fundamental approach towards disease epidemiology and the establishment of consistent prophylaxis and control measures. The objective of this study was to evaluate in vitro biofilm formation of a reference strain (L. interrogans, sv. Copenhageni L1 130 - L20) and of L. interrogans isolated from dogs (C20, C29, C51, C82), with subsequent evaluation of antimicrobial susceptibility in planktonic and biofilm forms. The semi quantification of biofilm production revealed a dynamic process of development over time, with mature biofilm formation early on the seventh day of incubation. All strains were efficient for in vitro biofilm formation and, in this form, they were considerably more resistant compared to their planktonic form, with MIC90 of 1600 µg/mL for amoxicillin, 800 µg/mL for ampicillin, and >1600 µg/mL for doxycycline and ciprofloxacin. The strains studies were isolated on naturally infected dogs that might act as reservoirs and sentinels for human infections. The potential to antimicrobial resistance together with the close relation between dogs and humans indicates the need for greater actions on disease control and surveillance. Moreover, biofilm formation may contribute to the persistence of Leptospira interrogans in the host and these animals can act as chronic carriers, disseminating the agent in the environment.

Factors related to the suppression of the antitumour immune response in female dogs with inflammatory mammary carcinoma.

Inflammatory mammary carcinoma (IMC), a neoplasia affecting women and female dogs, is considered an aggressive cancer with high metastatic potential and a low survival rate. Studies focused on the tumour microenvironment indicate that the aggressive behaviour of this tumour is primarily correlated with immunological factors as well as inflammation. The objective of this study was to analyse the possible strategies used by the tumour cells to suppress the immune response in female dogs with IMC. Forty-six female dogs were divided into three groups: control (C, n = 10), IMC (n = 14) and mammary carcinoma (MC, n = 22). Clinical-pathological evaluations, survival at follow-up, immunophenotyping of leukocytes in peripheral blood and tumours, and immunohistochemical evaluation of CD4+, granzyme B, perforin and FAS-L were performed. Clinical and pathological results showed a higher frequency of the primary form of neoplasia, solid arrays of tumor cells and a lower survival rate in the IMC group (30 days). Morphometric analysis of inflammatory infiltrate revealed more lymphocytes and macrophages in the IMC group. Immunophenotyping analysis of peripheral blood revealed a higher frequency of CD8+ T-cells (p = 0.0017), a lower frequency of CD4+ T-cells (p <0.0001), and significantly higher mean MHCI and MHCII CD14+ fluorescence intensity in the IMC group (p = 0.038 and p = 0.0117, respectively). The immunohistochemical evaluation of tumour sections showed fewer FAS-L-positive inflammatory cells in the IMC group. These results suggest the important contribution of CD8+ T-cells, macrophages and FAS-L in the aggressiveness of IMC.

Hyperresistinemia in Obese Female Dogs With Mammary Carcinoma in Benign-Mixed Tumors and Its Correlation With Tumor Aggressiveness and Survival.

Resistin is associated with metabolic, inflammatory, and neoplastic disorders, and is also considered a prognostic marker in human oncology. Canine mammary tumors have epidemiological, clinical, biological, and genetic characteristics similar to those of women and are proposed as a comparative study model. Here, we evaluate the serum levels of resistin in female dogs with or without mammary carcinoma in mixed tumors (CBMT) and its correlation with the proliferative potential of the tumor, obesity, and survival. Eighty dogs grouped according to the presence (50) or absence (30) of CBMT, reproductive status and body condition were assessed for weight, fat percentage, and canine body mass index. The characteristic of the proliferative potential of the tumor (Ki-67) was evaluated. Ki-67 levels (p = 0.024), staging (p = 0.004), and grade (p = 0.016) influenced the survival of the female dogs. Through a multifactorial analysis, it could be seen that the parameters proliferation index (Ki-67) (p = 0.044) and staging (p = 0.036) influenced the survival of the animals. Neutered and overweight dogs from the control and CBMT groups showed hyperresistinemia. Ki-67 expression and resistin levels in dogs with CBMT were higher in overweight dogs than in dogs with normal weight (p = 0.0001). The survival rate of dogs with CBMT, obese and with high levels of resistin (8,400 µg L-1) was lower when compared to those with lower levels of resistin. These results showed an important relationship between hyperresistinemia, tumor proliferative potential and excessive body fat, suggesting that resistin levels may act as an interesting prognostic marker in patients with CBMT.

Erratum to "Mixed tumors of the canine mammary glands: Evaluation of prognostic factors, treatment, and overall survival" [7C (June 2019) 100039].

[This corrects the article DOI: 10.1016/j.vas.2018.09.003.].

Triple-negative mammary carcinoma in two male dogs.

Triple-negative tumors are characterized immunohistochemically by the absence of positivity to sex hormone receptors and to human epidermal growth factor receptor 2. Additionally, they are differentiated into basal-like and non-basal (or null) subtypes, based on the presence of basal cytokeratin expression (CK5/6, 14, and17). Triple-negative subtypes are yet to be characterized in male dogs, to our knowledge. We report herein the clinical and pathologic findings and molecular characterization of carcinoma in the mammary glands of 2 male dogs. Case 1 was diagnosed as a grade II tubulopapillary carcinoma; case 2 was diagnosed as a grade II carcinoma in a mixed tumor. The tumors were characterized phenotypically as triple-negative basal and triple-negative non-basal, respectively.

Lipid and metabolic profiles in female dogs with mammary carcinoma receiving dietary fish oil supplementation.

BACKGROUND: Dyslipidemias induce angiogenesis and accelerate the development and in vitro growth of breast tumors. The aim of this study was to assess the lipid and metabolic profile of female dogs with mammary carcinomas and their correlations with body condition score and degree of tumor malignancy, as well as to study the effect of dietary fish oil supplementation on these animals. RESULTS: Overweight or obese dogs had more aggressive carcinomas and higher triglyceride (p = 0.0363), VLDL (p = 0.0181), albumin (p = 0.0188), globulin (p = 0.0145) and lactate (p = 0.0255) concentrations. There was no change in the lipid profile after supplementation with fish oil at any concentration. However, in relation to the metabolic profile, glucose (p = 0.0067), total protein (p = 0.0002) and globulin (p = 0.0002) concentrations were increased when 90% omega-3 fish oil was used as a dietary supplement. CONCLUSION: Obese dogs showed altered lipid and metabolic profiles and more aggressive tumors, suggesting an important relationship between dyslipidemia and tumor aggressiveness. Supplementation with fish oil, rich in omega-3 fatty acids, may alter metabolic parameters in cancer patients.

Versican and Tumor-Associated Macrophages Promotes Tumor Progression and Metastasis in Canine and Murine Models of Breast Carcinoma.

Versican and tumor-associated macrophages (TAMs) are involved in growth and metastases in several cancers. Here, we investigated the potential role of versican, a matrix proteoglycan, and its correlation with TAMs infiltrates in different stages of two different breast cancer models: spontaneous canine mammary gland carcinomas and the murine 4T1 breast cancer model. The stromal versican expression was correlated with TAMs accumulation in tumors with an advanced stage from spontaneous canine mammary carcinoma samples. Versican expression in mice, identified in late stages of tumor progression, was associated to a high number of peri-tumoral infiltrating TAMs. Indeed, TAMs were related to a pro-inflammatory and pro-angiogenic state in the primary tumor. Furthermore, TAMs accumulation was related to versican expression in the lungs and an increased number of pulmonary metastatic nodules with pulmonary mechanical dysfunction, which was due to leukocyte influx in the airways and elevated growth factor levels in the microenvironment. Thus, we suggest that versican and TAMs as attractive targets for breast cancer therapy.

Correction: The investigation of transcriptional repression mediated by ZEB2 in canine invasive micropapillary carcinoma in mammary gland.

[This corrects the article DOI: 10.1371/journal.pone.0209497.].

The investigation of transcriptional repression mediated by ZEB2 in canine invasive micropapillary carcinoma in mammary gland.

The E-cadherin loss has frequently been associated with transcriptional repression mediated by transcription factors, such as the Zinc Finger E-Box Binding Homeobox-2 (ZEB2). Invasive micropapillary carcinomas (IMPCs) of the breast are aggressive neoplasms frequently related to lymph node metastasis and poor overall survival. In the canine mammary gland, IMPCs has just been reported and, based on its behavioral similarity with the human IMPCs, appears to be a good spontaneous model to this human entity. This study aimed to evaluate the relationship between E-cadherin and ZEB2 in a spontaneous canine model of invasive micropapillary carcinoma of the mammary gland. The correlation among gene expression (ZEB2 and CDH1) and clinicopathological findings was also explored. Nineteen cases of IMPC of the canine mammary gland were obtained, protein and mRNA expression were investigated through immunohistochemistry and RNA In Situ Hybridization, respectively. To better understand the relationship between E-cadherin and ZEB2, immunofluorescence was performed in canine IMPCs. Immunohistochemically, most of IMPCs showed 1+ (14/19, 73.7%) for E-cadherin; and positivity for ZEB2 was diagnosed in 47.4% of the IMPCs. Regarding the RNA In Situ Hybridization (ISH), most of IMPCs showed 4+ and 0+ for E-cadherin (CDH1) and ZEB2 respectively. Through immunofluorescence, the first and second more frequent combinatorial group were E-cadherin+ZEB2- and E-cadherin+ZEB2+; neoplastic cells showing concomitantly weak expression for E-cadherin and positivity for ZEB2 were frequently observed. A negative correlation was observed between E-cadherin and progesterone receptor expression in IMPCs. Based on these results, canine mammary IMPCs show E-cadherin lost and, at times reveals nuclear positivity for the transcription factor ZEB2 that seems to exert transcriptional repression of the CDH1.

Mixed tumors of the canine mammary glands: Evaluation of prognostic factors, treatment, and overall survival.

Mixed tumors are the most frequent mammary gland neoplasms in bitches; however, studies that thoroughly describe their clinicopathological data, treatment approaches, and the survival of bitches with mixed tumors are scarce. This study evaluated the epidemiological and clinicopathological data, prognostic factors, and therapeutic approaches for bitches with mixed tumors. In all, 162 benign mixed tumors, 682 carcinomas in mixed tumors, and 60 carcinosarcomas were included. Regarding tumor size, T3 lesions were predominantly associated with carcinosarcomas, while T1 and T2 lesions occurred more frequently in benign mixed tumors and in carcinomas in mixed tumors. Based on clinical staging, most bitches with benign mixed tumors presented with stage I tumors; 92% of bitches with carcinomas in mixed tumors presented with stage I-III tumors, while 8% presented with stage IV-V tumors; and 70% of bitches with carcinosarcomas presented with stage I-III tumors, while 30% presented with stage IV-V tumors. Surgery was curative for bitches with benign mixed tumors and for those with stage I-III carcinomas in mixed tumors. Combination therapy in bitches with carcinomas in mixed tumors (IV-V) and carcinosarcomas resulted in a higher overall survival compared with bitches who underwent surgery only. Carcinosarcomas presented higher relapse rates and distant metastases than carcinomas in mixed tumors did.

Tumor-associated macrophage is correlated with survival and SOCS protein expression in canine mammary carcinoma / Correlação do infiltrado macrofágico com a sobrevida e a expressão da proteína SOCS no carcinoma mamário canino

The inflammatory infiltrate in the tumor microenvironment, particularly in mammary tumors, has aroused great interest in oncology, to play different roles in the progression or tumor regression dependent on the types and cell subsets involved. The present study aimed to evaluate (1) the occurrence and intensity of macrophage infiltration in the mammary carcinoma microenvironment, (2) the expression of SOCS1 and SOCS3 proteins in tumor associated macrophages, (3) any association between these parameters and tumor development, as well as survival rates in female dogs. Twenty-two female dogs diagnosed as carcinoma arising in a mixed tumor (CMT) by histopathology were divided into two groups following mastectomy: dogs without metastasis (CMT(-)=11) and those with metastasis (CMT(+)=11). The following parameters were analyzed: tumor size, lymph node metastasis, clinical stage, histological grade, distribution and intensity of inflammatory infiltrate, tumor macrophage quantification by immunohistochemical analysis of SOCS1 and SOCS3 expression, and immunophenotyping of peripheral blood leukocytes by flow cytometry. Dogs with the higher proportions of macrophages in the inflammatory infiltrate (≥400/tumor) also had higher survival rates in comparison with dogs with less macrophages. Immunostaining revealed higher proportions of SOCS3-positive macrophages in dogs without lymph node metastasis, while SOCS1-positive macrophages were predominant in dogs with metastasis (p<0.05). Multivariate analysis found associations between survival rate and clinical staging (p=0.025), histological grade (p=0.007), and the expression of MHC-CI in circulating monocytes (p=0.018). Higher SOCS3 expression in activated macrophages within the inflammatory infiltrate were considered indicative of an antitumor immune response, improved clinicopathological parameters and longer survival, whereas SOCS1-related activation was associated with tumor progression, metastasis development and reduced survival in female dogs with mammary carcinomas.(AU)

O infiltrado inflamatório no microambiente tumoral, particularmente nos tumores mamários, tem despertado grande interesse na oncologia, por desempenhar diferentes funções na progressão ou regressão tumoral, dependendo dos tipos e subtipos celulares envolvidos. O presente estudo teve como objetivo avaliar: (1) a ocorrência e a intensidade do infiltrado macrofágico no microambiente do carcinoma mamário; (2) a expressão das proteínas SOCS1 e SOCS3 nos macrófagos associados ao tumor; (3) qualquer associação relacionada ao prognóstico entre estes parâmetros e o desenvolvimento tumoral, assim como a taxa de sobrevida. Vinte e duas cadelas diagnosticadas com carcinoma em tumor misto (CTM) por exame histopatológico foram divididas em dois grupos após a mastectomia: cadelas sem metástase (CTM(-)=11) e cadelas com metástase (CTM(+)=11). Foram analisados os seguintes parâmetros: tamanho do tumor, metástase para linfonodo, estadiamento clínico, grau histológico, distribuição e intensidade do infiltrado inflamatório, quantificação dos macrófagos tumorais por análise imuno-histoquímica da expressão de SOCS1 e SOCS3, e imunofenotipagem dos leucócitos (monócitos e linfócitos) do sangue periférico por citometria de fluxo. Cadelas que apresentavam maiores proporções de macrófagos no infiltrado inflamatório (≥400/tumor) também tiveram maior taxa de sobrevida em comparação àquelas com menos macrófagos. A imunomarcação revelou maiores proporções de macrófagos SOCS3-positivos em cães sem metástase para linfonodo, enquanto que macrófagos SOCS1-positivos foram predominantes naqueles com metástase (p<0,05). A análise multivariada identificou associações entre a taxa de sobrevida e o estadiamento clínico (p=0,025), grau histológico (p=0,007) e a expressão de MHC-CI em monócitos circulantes (p=0,018). A maior expressão de SOCS3 nos macrófagos ativados foi considerada indicativa de uma resposta imune antitumoral, melhores parâmetros clínicos e maior taxa de sobrevida, ao passo que a ativação relacionada com SOCS1 foi associada à progressão tumoral, desenvolvimento de metástase e redução na taxa de sobrevida em cadelas com carcinoma mamário.(AU)

Expression of epidermal growth factor receptor (EGFR) in cholangiocarcinomas: predictive factors and survival.

OBJECTIVE: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. METHODS: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. RESULTS: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. CONCLUSION: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.

Consensus for the diagnosis, prognosis and treatment of feline mammary tumors / Consenso para o diagnóstico, prognóstico e tratamento de tumores mamários em felinos

Mammary neoplasms are described as the third most common type of feline tumor, after haematopoietic and skin tumors, and present a challenge for clinicians because the prognosis for feline mammary tumors ranges from guarded to poor. Thus, it is necessary to define new therapeutic approaches and establish more in-depth knowledge about this disease in felines. The main aspects of the diagnosis, prognosis and treatment of feline mammary neoplasia were discussed, aiming to standardize the criteria and to serve as a guide for pathologists and veterinary clinicians.(AU)

As neoplasias mamárias são descritas como o terceiro tipo mais frequente de tumor em felinos (após as neoplasias hematopoiéticas e cutâneas) e apresentam um desafio para os clínicos devido ao prognóstico, que varia de reservado a ruim. Assim, é necessário conhecer melhor essa doença em felinos e definir novas abordagens terapêuticas. Discutiu-se os principais aspectos de diagnóstico, prognóstico e tratamento da neoplasia mamária felina, com o objetivo de padronizar os critérios e servir de guia para patologistas e clínicos veterinários.(AU)

Expression of epidermal growth factor receptor (EGFR) in cholangiocarcinomas: predictive factors and survival / Expressão do receptor do fator de crescimento epitelial (EGFR) em colangiocarcinomas: fatores preditivos e sobrevida

ABSTRACT Objective: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. Methods: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. Results: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. Conclusion: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.

RESUMO Objetivo: avaliar a expressão do receptor do fator de crescimento epitelial (EGFR) por meio de imuno-histoquímica, e verificar sua associação com fatores prognósticos e com a sobrevida dos pacientes operados por colangiocarcinoma. Métodos: a expressão imuno-histoquímica de EGFR foi verificada em 35 peças cirúrgicas de colangiocarcinomas (CCA). Curvas de sobrevida foram obtidas pelo método de Kaplan-Meier. Resultados: expressão significativa de EGFR foi encontrada em dez (28,6%) de 35 CCA, oito com escore 3 e dois com escore 2. Estágios avançados (III e IV) apresentaram maior expressão de EGFR (p=0,07). As características clínicas que mais estiveram associadas com a expressão positiva de EGFR foram o sexo feminino (p=0,06) e ausência de comorbidades (p=0,06). A sobrevida global aos 12, 24, 36 e 48 meses foi de 100%, 82,5%, 59% e 44,2%, respectivamente. A sobrevida de pacientes EGFR positivos aos 12, 24, 36 e 48 meses foi de 100%, 75%, 50% e 0%, enquanto que para EGFR negativos foi de 100%, 87,5%, 65,6% e 65,6%, respectivamente. Conclusão: a expressão do EGFR ocorreu em 28,6% dos casos estudados e esteve associada a menor sobrevida.

Multicentric lymphoma in buffaloes in the Amazon region, Brazil.

BACKGROUND: The presence of lymphoma in buffaloes was first reported in India in the 1960s. The disease is similar to Enzootic Bovine Leucosis (EBL) caused by Bovine leukemia virus (BLV) in cattle; however, according to our results and those of other studies, the etiology of these lymphomas in buffalo do not appear to be associated with BLV. The objectives of this study are to describe four cases of the disease in buffaloes belonging to the same herd in the Amazon region of Brazil and to perform a clinical-anatomopathological, immunohistochemical, and etiological study of the lymphomas. RESULTS: Over a period of ten years, four buffaloes were observed presenting progressive weight loss, swelling of peripheral lymph nodes, and nodules in the subcutaneous tissue. Upon necropsy, whitish-colored tumor masses were observed in the form of nodules in the subcutaneous tissue, along with miliary nodules on the serosal surfaces of abdominal and thoracic organs and tumors in lymph nodes and other organs. Neoplastic lymphocyte proliferation was observed through histopathology. An immunohistochemical study revealed that the neoplasias were formed by proliferation of predominantly B lymphocytes. The presence of BLV genome was not detected in the lymphomas when using the real-time PCR technique, nor was it detected through immunohistochemical staining using monoclonal antibodies against two viral proteins. Bovine herpesvirus 6 was not detected in the tumors. However, Bovine immunodeficiency virus (BIV) was detected in samples of lymphoma and in the lymph nodes and kidneys of one of the animals. CONCLUSIONS: The occurrence of lymphoma in buffaloes is reported for the first time in Brazil and is characterized by B-cell multicentric lymphoma. The etiology of the disease does not appear to be associated with BLV; however, the detection of BIV in samples of lymphoma from one sick animal deserves further study, considering the oncogenic potential of this virus.

HER-2 and EGFR mRNA Expression and Its Relationship with Versican in Malignant Matrix-Producing Tumors of the Canine Mammary Gland.

Versican expression promotes tumor growth by destabilizing focal cell contacts, thus impeding cell adhesion and facilitating cell migration. It not only presents or recruits molecules to the cell surface, but also modulates gene expression levels and coordinates complex signal pathways. Previously, we suggested that the interaction between versican and human epidermal growth factor receptors may be directly associated with tumor aggressiveness. Thus, the expression of EGFR and HER-2 in these neoplasms may contribute to a better understanding of the progression mechanisms in malignant mammary tumors. The purpose of this study was to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their relationship with the versican expression in carcinomas in mixed tumors and carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA expression showed a significant difference between in situ and invasive carcinomatous areas in low and high versican expression groups. Identical results were observed in HER-2 mRNA expression. In immunohistochemistry analysis, neoplasms with low versican expression showed greater EGFR immunostaining in the in situ areas than in invasive areas, even as the group presenting high versican expression displayed greater EGFR and HER-2 staining in in situ areas. Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous sites relative to invasive areas suggest that these molecules play a role during the early stages of tumor progression.

Evaluation of prognostic factors and survival rates in malignant feline mammary gland neoplasms.

OBJECTIVES: The aim of the study was to investigate prognostic factors in feline mammary gland neoplasms, correlating them with overall survival (OS). METHODS: Fifty-six primary malignant mammary gland neoplasms and 16 metastatic lymph nodes from 37 female cats were analyzed. Clinical staging, histologic type and grade, and immunohistochemistry for Ki-67, progesterone and estrogen receptor, human epidermal growth factor receptor type 2 (HER-2), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were evaluated. Follow-up was performed in order to correlate prognostic factors with OS. RESULTS: Lymph node metastasis was found in 35% of cases. Clinical stage III, tubulopapillary carcinomas and histologic grade II cases prevailed in the study. Most neoplasms were positive for hormonal receptors, negative for HER-2 overexpression and presented VEGF overexpression. Immunoreactivity for Ki-67 (P = 0.046) and COX-2 (P = 0.007) was higher in metastases than in primary tumors. COX-2 (P = 0.089), HER-2 (P = 0.012) and histologic grade (P = 0.080) were correlated with OS. CONCLUSIONS AND RELEVANCE: The data suggest that inhibition of ovarian hormones and COX-2 may represent a therapeutic option for malignant feline mammary gland neoplasms. When evaluating disease progression, COX-2 scores and Ki-67 index should be analyzed in primary tumors and metastases. Histologic grade, HER-2 status and COX-2 scores were found to have a direct influence on OS. Prognostic factors allow for a better understanding of disease outcome in a condition that is characterized by a poor prognosis. The present work highlights the need for further studies on endocrine therapy and COX-2 inhibitors, which could influence OS.

Malignant peripheral nerve sheath tumour in a sow.

Nodular lung lesions in swine are frequently due to abscesses or granulomatous pneumonia. Although tumours are rarely reported in modern pig farming, they should be considered as a differential diagnosis when nodular lung lesions are found. A first-parity sow exhibiting respiratory signs was euthanized. Several whitish firm nodules, not encapsulated, ranging in diameter from 0.5 to 5 cm were present in all lung lobes. Microscopically, the nodules were composed of dense neoplastic cells, mainly in Antoni types A and B patterns, infiltrative and with development of emboli. All neoplastic cells stained positively by immunohistochemistry for vimentin and S-100 protein, with variable immunostaining for glial fibrillary acidic protein and stained negative for cytokeratin. Based on the gross, histological and immunohistochemical features, the tumor was diagnosed as malignant peripheral nerve sheath tumour.

Cytologic analysis of the mammary papillar discharge in a canine micropapillary carcinoma.

This is a report on the cytologic analysis of the mammary papillar discharge in a 7-year-old female Doberman dog with an invasive micropapillary carcinoma. Cytologic evaluation of nipple discharge is a well-known method for the rapid diagnosis of breast cancer in women. However, there is no previous report regarding the use of this technique for assessing mammary tumors in dogs. The aim of this study was to describe the use of mammary papillar discharge cytology for diagnosing a micropapillary carcinoma in a dog. Cytologically, evaluation of the papillar discharge revealed cells arranged in clusters in a papillary pattern or in a morula-like arrangement, suggesting the diagnosis of a micropapillary carcinoma, which was subsequently confirmed by histopathology. Thus, mammary papillar discharge cytology should be considered as an ancillary method for evaluating mammary diseases in dogs.