Immunohistochemical panel to characterize canine prostate carcinomas according to aberrant p63 expression.

An unusual variant of prostate adenocarcinoma (PC) expressing nuclear p63 in secretory cells instead of the typical basal expression has been reported in men. Nevertheless, the biological behavior and clinical significance of this phenomenon is unknown. In dogs, this unusual PC subtype has not been described. In this study, p63 immunoexpression was investigated in 90 canine PCs and 20 normal prostate tissues (NT). The p63 expression pattern in luminal or basal cells was confirmed in a selected group of 26 PCs and 20 NT by immunohistochemistry and/or Western blotting assays. Eleven canine PC samples aberrantly expressing p63 (p63+) in secretory cells were compared with 15 p63 negative (p63-) cases in the context of several molecular markers (high molecular weight cytokeratin-HMWC, CK8/18, CK5, AR, PSA, chromogranin, NKX3.1, PTEN, AKT and C-MYC). P63+ samples were positive for CK5, HMWC and CK8/18 and negative for PSA, NKX3.1, PTEN and chromogranin. Five p63+ PCs were negative for AR, and the remaining six samples had low AR expression. In contrast, p63- PC showed AR and PSA positive expression in all 15 samples. Only five p63- PCs were positive for CK5. Both p63+ and p63- PC samples showed higher cytoplasmic AKT expression and nuclear C-MYC staining in comparison with normal tissues. Metastatic (N = 12) and non-metastatic (N = 14) PCs showed similar immunoexpression for all markers tested. In contrast to human PC, canine PC aberrantly expressing p63 showed higher expression levels of HMWC and CK5 and lower levels of NKX3.1. Canine p63+ PC is a very rare PC group showing a distinct phenotype compared to typical canine PC, including AR and PSA negative expression. Although in a limited number of cases, p63 expression was not associated with metastasis in canine PC, and cytoplasmic p63 expression was observed in animals with shorter survival time, similar to human PC cases.

Alterations in PTEN, MDM2, TP53 and AR protein and gene expression are associated with canine prostate carcinogenesis.

The PTEN, AR, MDM2 and p53 protein network plays a central role in the development of many human cancers, thus eliciting the development of targeted cancer therapeutics. Dogs spontaneously develop tumours, and they are considered a good model for comparative oncology initiatives. Due to the limited information on these proteins in canine tumours, this study aimed to investigate gene and protein alterations in PTEN, AR, MDM2 and p53 in canine prostate cancer (PC). Protein expression was evaluated by immunohistochemistry (15 normal, 22 proliferative inflammatory atrophy (PIA) and 19 PC samples) and Western blotting (2 normal prostate tissue, 2 BPH, 2 PIA samples and 2 PC samples) and gene expression by RT-qPCR (10 normal, 10 PIA and 15 PC samples) of formalin-fixed tissue. We identified nuclear and cytoplasmic expression of PTEN and p53 in all samples, with only nuclear staining found for MDM2 and AR. Our results revealed high expression of MDM2 in PC and PIA samples compared to normal samples, whereas PTEN, P53 and AR expression was down-regulated in PC compared to normal tissue. All tumour samples (n=19) showed loss of nuclear PTEN expression, and all cancer mimickers showed positive nuclear staining. Therefore, nuclear PTEN staining could be a good diagnostic marker for differentiating between malignant lesions and mimickers. Canine prostate carcinogenesis involves increased expression of MDM2 in association with decreased expression of PTEN, p53 and AR, such as occurs in hormone refractory PC in men. Thus, dogs may be an important model for studying advanced stage PC.

Evidence of epithelial-mesenchymal transition in canine prostate cancer metastasis.

The epithelial-mesenchymal transition (EMT) is a fundamental event responsible for the invasiveness and metastasis of epithelial tumours. The EMT has been described in many human cancers, but there are few reports of this phenomenon in veterinary oncology. Due to the importance of this process, the current study evaluated mesenchymal and epithelial marker protein expression in prostate lesions from dogs. Our results indicate both a loss of E-cadherin and translocation of ß-catenin from the membrane to the cytoplasm and nucleus in the tumour group. Vimentin expression in the tumour group was higher than in normal tissue. All of the metastases were positive for prostate-specific antigen, pan-cytokeratin and E-cadherin, although fewer positive cells were present than in the primary tumours. The immunohistochemical results showed a loss of epithelial markers and a gain of a mesenchymal marker among metastatic cells, suggesting that the EMT occurs during the metastatic process of canine prostate carcinoma.

Bilateral canine seminoma with ocular metastasis: histochemical and immunohistochemical characterization

A 10-year old male dog was examined due to a buphthalmia in the left eye and a nodule in the two testicles. Due to the limited resources of the owner and loss of visual acuity of the patient, the enucleation and castration were chosen as treatment. Microscopic analysis of the testicular tissue revealed neoplastic germ cells. Morphologically, neoplastic cells were characterized by distinct cell borders, scarce and eosinophilic cytoplasm, large round nucleus, with thick chromatin and a prominent nucleolus. Binucleated and multinucleated neoplastic cells were also frequently observed. In 10 high powerfields (400x), 62 typical and atypical mitosis were counted. Similar neoplastic cells were identified within the vessels of theretina, sclera and in the sub-epithelial conjunctive tissue of the eyelid. The neoplastic cells observed in the testicle and in the eye were positive for PAS. By immunochemistry technique was identified an intense immunostaining of the neoplastic cells for Vimentin and Ki-67 in both testicular and ocular tissue. While, discrete immunoreactivity was identified to c-KIT from the neoplastic cells in both organs. Based on morphological, histochemical and immunohistochemical analysis, it was possible to characterize the ocular lesion as seminoma metastasis.

Bilateral canine seminoma with ocular metastasis: histochemical and immunohistochemical characterization

A 10-year old male dog was examined due to a buphthalmia in the left eye and a nodule in the two testicles. Due to the limited resources of the owner and loss of visual acuity of the patient, the enucleation and castration were chosen as treatment. Microscopic analysis of the testicular tissue revealed neoplastic germ cells. Morphologically, neoplastic cells were characterized by distinct cell borders, scarce and eosinophilic cytoplasm, large round nucleus, with thick chromatin and a prominent nucleolus. Binucleated and multinucleated neoplastic cells were also frequently observed. In 10 high powerfields (400x), 62 typical and atypical mitosis were counted. Similar neoplastic cells were identified within the vessels of theretina, sclera and in the sub-epithelial conjunctive tissue of the eyelid. The neoplastic cells observed in the testicle and in the eye were positive for PAS. By immunochemistry technique was identified an intense immunostaining of the neoplastic cells for Vimentin and Ki-67 in both testicular and ocular tissue. While, discrete immunoreactivity was identified to c-KIT from the neoplastic cells in both organs. Based on morphological, histochemical and immunohistochemical analysis, it was possible to characterize the ocular lesion as seminoma metastasis.(AU)

Proceso carcinogenico de las próstatas caninas: via WNT canónica y su estudio comparado / Carcinogenic process of canine prostate: WNT canonical pathway and its comparative study / Processo carcinogênico das próstatas caninas: via WNT canônica e seu estudo comparado

La especie canina presenta semejanza con la especie humana con relación a las lesiones prostáticas. Es la única especie en presentar tumores espontáneos con frecuencia, de esta manera representa un importante modelo para estudio comparativo de afecciones de la glándula. El desarrollo de las neoplasia prostáticas es una enfermedad con causas multifactoriales, entre estas, alteraciones genéticas y epigenéticas están involucradas. Por lo tanto, el perro puede ser un modelo natural y espontaneo para el estudio de lesiones preneoplásicas e neoplásicas de próstata canina. En el futuro, podrá ser utilizado como modelo en pruebas pre-clínicas de medicamentos, como ya fue realizado para osteosarcoma, por ejemplo. Una de las vías importantes para el desarrollo de los carcinomas prostáticos es la WNT canónica dependiente de la proteína Beta-catenina. En esta revisión abordaremos el papel de esta vía y su participación en la carcinogénesis prostática, importante en humanos y perros, además de algunas proteínas involucradas en la regulación de la misma.

Prostate of dogs have similar lesions to that observed in human and is the only species other than man which frequently displays spontaneous prostatic tumors. In this way, the dog represent an important model of studying different prostatic affections. The prostate cancer development is multifactorial and among them, genetic and epigenetic alterations are involved. The dog can be a natural and spontaneous model to study preneoplastic and neoplastic lesions, with potential future studies as models for pre-clinical tests. One of important pathway to prostate carcinogenesis is beta catenin dependent canonical WNT pathway. In this paper, we review the role of this pathway in prostate carcinogenesis, important in humans and dogs, besides some regulatory proteins involved in this pathway.

A espécie canina apresenta semelhanças com a espécie humana com relação às lesões prostáticas, sendo a única espécie a apresentar tumores espontâneos e com frequência, desse modo representa um importante modelo para estudo comparativo de afecções desta glândula. O desenvolvimento das neoplasias prostáticas é multifatorial e dentre eles, alterações genéticas e epigenéticas estão envolvidas, portanto o cão pode ser um modelo natural e espontâneo para o estudo das lesões pré neoplásicas e neoplásicas da próstata, com futuro alto potencial de ser utilizado como modelo em testes pré-clínicos de medicamentos. Uma das vias importantes para o desenvolvimento dos carcinomas prostáticos é a WNT canônica, dependente da proteína Beta-catenina. Nesta revisão, abordaremos o papel desta via e sua participação na carcinogênese prostática, importante em humanos e cães, além de algumas proteínas envolvidas na regulação da mesma.

Proceso carcinogenico de las próstatas caninas: via WNT canónica y su estudio comparado / Carcinogenic process of canine prostate: WNT canonical pathway and its comparative study / Processo carcinogênico das próstatas caninas: via WNT canônica e seu estudo comparado

La especie canina presenta semejanza con la especie humana con relación a las lesiones prostáticas. Es la única especie en presentar tumores espontáneos con frecuencia, de esta manera representa un importante modelo para estudio comparativo de afecciones de la glándula. El desarrollo de las neoplasia prostáticas es una enfermedad con causas multifactoriales, entre estas, alteraciones genéticas y epigenéticas están involucradas. Por lo tanto, el perro puede ser un modelo natural y espontaneo para el estudio de lesiones preneoplásicas e neoplásicas de próstata canina. En el futuro, podrá ser utilizado como modelo en pruebas pre-clínicas de medicamentos, como ya fue realizado para osteosarcoma, por ejemplo. Una de las vías importantes para el desarrollo de los carcinomas prostáticos es la WNT canónica dependiente de la proteína Beta-catenina. En esta revisión abordaremos el papel de esta vía y su participación en la carcinogénesis prostática, importante en humanos y perros, además de algunas proteínas involucradas en la regulación de la misma.(AU)

Prostate of dogs have similar lesions to that observed in human and is the only species other than man which frequently displays spontaneous prostatic tumors. In this way, the dog represent an important model of studying different prostatic affections. The prostate cancer development is multifactorial and among them, genetic and epigenetic alterations are involved. The dog can be a natural and spontaneous model to study preneoplastic and neoplastic lesions, with potential future studies as models for pre-clinical tests. One of important pathway to prostate carcinogenesis is beta catenin dependent canonical WNT pathway. In this paper, we review the role of this pathway in prostate carcinogenesis, important in humans and dogs, besides some regulatory proteins involved in this pathway.(AU)

A espécie canina apresenta semelhanças com a espécie humana com relação às lesões prostáticas, sendo a única espécie a apresentar tumores espontâneos e com frequência, desse modo representa um importante modelo para estudo comparativo de afecções desta glândula. O desenvolvimento das neoplasias prostáticas é multifatorial e dentre eles, alterações genéticas e epigenéticas estão envolvidas, portanto o cão pode ser um modelo natural e espontâneo para o estudo das lesões pré neoplásicas e neoplásicas da próstata, com futuro alto potencial de ser utilizado como modelo em testes pré-clínicos de medicamentos. Uma das vias importantes para o desenvolvimento dos carcinomas prostáticos é a WNT canônica, dependente da proteína Beta-catenina. Nesta revisão, abordaremos o papel desta via e sua participação na carcinogênese prostática, importante em humanos e cães, além de algumas proteínas envolvidas na regulação da mesma.(AU)

Resistance of Salmonella to conventional antimicrobials for theirtreatment / Resistencia de la Salmonela a los antimicrobianos convencionales para sutratamiento / Resistência da Salmonela aos antimicrobianos convencionais para seu tratamento

Resistance is the mechanism by which the bacteria can lower the action of the agents antimicrobials of form naturalor acquired; within the most frequent causes is the indiscriminate use of these agents in patients humans and cattleproduction. Since 1990, have been identified news strains of bacteria that cause emerging zoonotic diseases. Inside of these zoonosis, the salmonellosis is considered the disease more diffused at word level, the wide distribution innature between wildlife, domestics animals and the environment has generated a quick propagation of their more than 2500 serotypes in humans. However, the great preoccupation for infection with this enteropathogen is due to the increasingly in treatment failures with conventional antimicrobials, caused by the high bacterial resistance to thesedrugs. The present article is a review of the problems that it has developed resistance to Salmonella in humans andanimals; further contains strategies for prevention and control of this phenomenon, which although is far from over, allow strengthen the public health.

La resistencia es el mecanismo mediante el cual la bacteria puede disminuir la acción de los agentes antimicrobianos de forma natural o adquirida; dentro de las causas más frecuentes está la utilización indiscriminada de estos agentesen pacientes humanos y producciones pecuarias. Desde 1990 se han identificado nuevas cepas resistentes de bacterias que han originado enfermedades zoonóticas emergentes. Dentro de estas zoonosis, la salmonelosis es consideradala enfermedad más difundida a nivel mundial, la amplia distribución en la naturaleza entre animales silvestres,domésticos y el medio ambiente, produce una rápida propagación de sus más de 2500 serotipos en el hombre.Sin embargo, la gran preocupación por la infección con este entero patógeno se debe a los cada vez más elevadosfracasos en los tratamientos con antimicrobianos convencionales, ocasionados por la alta resistencia bacteriana a estos fármacos. El presente artículo es una revisión sobre la problemática que ha generado la resistencia de Salmonellaen el hombre y los animales, contiene además estrategias de prevención y control de este fenómeno, que si bien está lejos de terminar permiten el fortalecimiento de la salud pública.

A resistência é o mecanismo pelo qual a bactéria pode diminuir a ação dos agentes antimicrobianos de formanatural ou adquirida; dentro das causas mais frequentes está a utilização indiscriminada destes agentes em pacientes humanos e produções pecuárias. Desde 1990 tem identificado novas cepas resistentes de bactérias que originaram doenças zoonóticas emergentes. Dentro destas a zoonose, a salmonelose é considerada a doença mais difundida anível mundial, a ampla distribuição na natureza entre animais silvestres, domésticos e o meio ambiente, produz uma rápida propagação de seus mais de 2500 sorotipos no homem. Contudo, a grande preocupação pela infecção com este inteiro patógeno é devido aos cada vez mais elevados fracassos nos tratamentos com antimicrobianos convencionais,ocasionados pela alta resistência bacteriana a estes fármacos. O presente artigo é uma revisão sobre a problemáticaque gerou a resistência de Salmonella no homem e os animais, contem também estratégias de prevenção e controledeste fenômeno, que está distante de terminar e permitem o fortalecimento da saúde pública.