RESUMEN
A 4-month-old puppy died after showing intracranial signs a few days after a suspected viral enteritis. Grossly, the right cerebral hemisphere had a large irregular cavity external to the internal capsule. Histopathological examination revealed a cystic lesion in the right hemisphere and non-suppurative inflammation of the diencephalon and periaqueductal nervous tissue. Porencephaly associated with periventricular non-suppurative encephalitis was diagnosed. A nested polymerase chain reaction (PCR) identified the presence of parvovirus DNA in the brain and real-time PCR typed this as canine parvovirus (CPV) type 2a. Immunohistochemistry revealed the presence of CPV antigen in the cytoplasm of scattered cells in the subependymal layers and choroid plexus epithelium. The porencephaly was not associated with inflammatory lesions or CPV antigen and was considered to have preceded the neurological signs. In contrast, the detection of CPV antigen in the subependymal layers and choroid plexus epithelium supported the association of this virus with the periventricular encephalitis.
Asunto(s)
Enfermedades de los Perros/patología , Enfermedades de los Perros/virología , Encefalitis Viral/veterinaria , Infecciones por Parvoviridae/veterinaria , Porencefalia/veterinaria , Animales , Perros , Femenino , Parvovirus CaninoRESUMEN
The neuropeptide somatostatin (SST) plays an important regulatory role in the proliferation of normal and neoplastic cells. Five subtypes of somatostatin receptors (SSTRs), SSTR1-SSTR5, have been identified in human tumours. The SSTR2 subtype is identified most commonly in meningiomas. Long half-life SST analogues are now recommended for the systemic treatment of unresectable or radiation-refractory recurrent human meningiomas. In this study, SSTR2 expression was evaluated in 46 canine meningiomas; in 21 cases this was by immunohistochemistry and in 25 cases by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). In addition, SSTR2 expression was evaluated by immunocytochemistry, western blotting and RT-qPCR on primary cell cultures prepared from two canine meningiomas. SSTR2 immunohistochemical expression was observed in 17/21 cases (81%), and SSTR2 mRNA expression was detected in 14/25 cases (56%). SSTR2 protein and gene expression were not significantly correlated with the tumour histological subtype or grade. Overall, meningothelial meningiomas showed constant and diffuse SSTR2 immunohistochemical expression and the highest SSTR2 gene expression level compared with other subtypes. A tendency for loss of SSTR2 in high-grade meningiomas was observed in both immunohistochemical and RT-qPCR studies. About 90% of cultured canine meningioma cells showed SSTR2 expression. In both of the meningioma cell cultures, SSTR2 expression was also detected by western blotting and RT-qPCR. This study demonstrates for the first time that canine meningioma expresses SSTR2 and that this expression is maintained in vitro. Our results, while preliminary, provide encouragement for further studies aimed at finding novel medical treatment strategies for canine meningioma, especially for tumours that are not surgically accessible.
Asunto(s)
Enfermedades de los Perros/metabolismo , Neoplasias Meníngeas/veterinaria , Meningioma/veterinaria , Receptores de Somatostatina/biosíntesis , Animales , Perros , Femenino , MasculinoRESUMEN
BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are considered to be key mediators of tumor invasion and metastasis. MMP-2 and MMP-9 are expressed in meningiomas of dogs, but TIMP expression, and variations of specific MMP/TIMP ratios still are unknown in this tumor. HYPOTHESIS/OBJECTIVES: Expression of MMP/TIMP might increase progressively from grade I to grade III meningioma. Therefore, genetic expression of MMP-2 and MMP-9, and specific TIMP-2 and TIMP-1, respectively, has been investigated in meningiomas of different grades. ANIMALS: Selected formalin-fixed paraffin-embedded tissue from 43 meningiomas of dogs was evaluated. METHODS: Genetic material was obtained from pathologic samples and used for quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR). RESULTS: MMP-9 was not expressed in all of the tumors, but MMP-2 was significantly more expressed in papillary meningioma. Likewise, the MMP-2/TIMP-2 ratio was numerically higher in papillary meningiomas compared to all grades (>3.5 times) showing a strong bias in favor of metalloproteinase. In the papillary meningioma, TIMP-1 gene expression was significantly higher than in grades I and III. CONCLUSIONS AND CLINICAL IMPORTANCE: MMP-2/TIMP-2 imbalance might contribute to the aggressive biologic behavior of papillary meningiomas in dogs. TIMP-1 expression may play a role independent of MMP-9 expression in neoplastic progression. These results further support that therapeutic and prognostic evaluations of dogs with meningioma need to be addressed according to different histologic patterns as is performed in humans.
Asunto(s)
Enfermedades de los Perros/genética , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Meningioma/veterinaria , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-2/genética , Animales , Enfermedades de los Perros/metabolismo , Perros , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Meningioma/metabolismo , Meningioma/patología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismoRESUMEN
Choroid plexus tumors (CPTs) are reported with an increasing incidence in dogs, and they call for a reexamination of histologic features and criteria of classification corresponding to their biological behavior. In this study, the human World Health Organization classification was applied to 16 canine CPTs, and the expression of molecules involved in neoplastic cell adhesion (E-cadherin, N-cadherin), invasion (doublecortin), and proliferation (Ki-67) was investigated. Mitotic index was found to be the main criterion for grading CPTs. Cell density and multilayering of papillae were also statistically associated with histologic grade. Intraventricular spread and parenchymal invasion was observed for tumors showing histologic benign features. E-cadherin was expressed in all CPT grades, independent of tumor invasion. N-cadherin immunolabeling was more expressed in grade I than high-grade CPTs, whereas doublecortin expression was not detected in CPTs. An increasing proliferative activity was observed in relation with histologic grade.