Correlation of tumor-infiltrating lymphocytes to histopathological features and molecular phenotypes in canine mammary carcinoma: A morphologic and immunohistochemical morphometric study.

Abundant lymphocyte infiltration is frequently found in canine malignant mammary tumors, but the pathological features and immunophenotypes associated with the infiltration remain to be elucidated. The aim of the present study was to evaluate the relationship between lymphocyte infiltration, histopathological features, and molecular phenotype in canine mammary carcinoma (MC). The study was done with archived formalin-fixed, paraffin-embedded samples (n = 47) by histologic and immunohistochemical methods. The degree of lymphocyte infiltration was evaluated by morphologic analysis, and the T- and B-cell populations as well as the T/B-cell ratio were evaluated by morphometric analysis; results were compared with the histologic features and molecular phenotypes. The degree of lymphocyte infiltration was significantly higher in MCs with lymphatic invasion than in those without lymphatic invasion (P < 0.0001) and in tumors of high histologic grade compared with those of lower histologic grade (P = 0.045). Morphometric analysis showed a larger amount of T-cells and B-cells in MCs with a higher histologic grade and lymphatic invasion, but the T/B ratio did not change. Lymphocyte infiltration was not associated with histologic type or molecular phenotype, as assessed from the immunohistochemical expression of epidermal growth factor receptor 2, estrogen receptor, cytokeratin 14, and p63. Since intense lymphocyte infiltration was associated with aggressive histologic features, lymphocytes may be important for tumor aggressiveness and greater malignant behavior in the tumor microenvironment.

Une infiltration lymphocytaire abondante est fréquemment retrouvée dans les tumeurs mammaires malignes chez le chien, mais les caractéristiques pathologiques et les immunophénotypes associés avec l'infiltration restent à être élucidés. L'objectif de la présente étude était d'évaluer la relation entre l'infiltration lymphocytaire, les caractéristiques histopathologiques, et le phénotype moléculaire dans les carcinomes mammaires canins (CM). Cette étude a été réalisée en utilisant des méthodes histologiques et immunohistochimiques sur des échantillons archivés fixés à la formaline et enrobés de paraffine (n = 47). Le degré d'infiltration lymphocytaire a été évalué par analyse morphologique, et les populations de lymphocytes T et B ainsi que le ratio de cellules T/B ont été évalués par analyses morphométriques; les résultats ont été comparés avec les caractéristiques histologiques et les phénotypes moléculaires. Le degré d'infiltration lymphocytaire était significativement plus élevé dans les CM avec invasion lymphatique que dans ceux sans invasion lymphatique (P < 0,001) et dans les tumeurs de grade histologique élevé comparativement à ceux avec un grade histologique faible (P = 0,045). Les analyses morphométriques ont montré une quantité plus grande de cellules T et B dans les CM ayant un grade histologique élevé et invasion lymphatique, mais le ratio T/B n'a pas changé. L'infiltration lymphocytaire n'était pas associée avec le type histologique ou le phénotype moléculaire, tel qu'évalué par l'expression immunohistochimique du récepteur 2 du facteur de croissance épidermique, du récepteur d'estrogène, de cytokératine 14, et de p63. Étant donné que l'infiltration lymphocytaire marquée était associée avec des caractéristiques histologiques d'agressivité, les lymphocytes pourraient être importants pour l'agressivité des tumeurs et le comportement de malignité plus important dans le microenvironnement de la tumeur.(Traduit par Docteur Serge Messier).

Inflammatory mammary carcinoma with metastasis to the brain and distant organs in a spayed Shih Tzu dog.

Inflammatory mammary carcinoma (IMC) is a specific type of rare, very aggressive, and highly metastatic mammary cancer in both human beings and dogs. A 10-year-old female spayed Shih Tzu dog was diagnosed with secondary IMC. At necropsy, brain metastasis of mammary neoplastic cells was observed in tissues of the cerebrum and cerebellum. Metastases were also found in other distant organs such as heart, lung, liver, spleen, and inguinal lymph node. There is limited data about the metastasis of IMC and its pattern. The current report of IMC with brain metastases contributes to the understanding of metastatic IMC.

Pro- and anti-inflammatory cytokine expression and histopathological characteristics in canine brain with traumatic brain injury.

We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-ß)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1ß and TGF-ß. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines.

Histopathological retrospective study of canine renal disease in Korea, 2003~2008.

Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson's trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations.

Effects of Safflower seed oil in osteoporosis induced-ovariectomized rats.

The effects of Korean Safflower (Carthamus tinctorius L) seed oil (SSO) on osteoporosis induced-ovariectomized rats were investigated. A total of 90 female Sprague-Dawley rats, 4-month-old, weighing 200-230 g were randomly assigned into 3 groups (30 animals/group). The animals in group I were sham operated and those of group II and III were ovariectomized (Ovx). After eight weeks, the animals of group I and II received solvent vehicle daily, whereas those of group III were administered SSO orally (1 ml/kg) daily for 30 days. The changes in the serum levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth factor binding protein-3 (IGBP-3), estrogen, total alkaline phosphatase (TALP), bone-specific alkaline phosphatase (BALP), calcium and phosphorous in serum, and also the histomorphology of the proximal tibia metaphysis and femur/body weight (F/B) ratio were examined in all the groups at every 10 days interval. Thirty days later, IGF-I, IGF-II, IGBP-3 and BALP levels were significantly increased (p < 0.05) in group III as compared to groups I and II. There were no significant differences in serum levels of estrogen, TALP and F/B ratio between groups II and III, but estrogen levels were higher in group I. These results suggest that the safflower seeds have possible roles in the improvement of osteoporosis induced-ovariectomized rats.

Evaluation of silymarin in the treatment on asymptomatic Giardia infections in dogs.

We have reported previously the efficacy of antiprotozoal drugs against canine giardiasis (In press, Journal of Veterinary Clinic, the Korean Society of Veterinary Clinics). Fenbendazole was found to be the most efficacious for the treatment of canine giardiasis. There were no significant differences between the efficacy of albendazole and fenbendazole against canine giardiasis. On the other hand, the efficacy of metronidazole for the treatment of canine giardiasis, the efficacy was lower when compared to that of albendazole and fenbendazole. On the basis of these results, to evaluate clinical effect of silymarin, we evaluated the therapeutic efficacy of metronidazole alone, or combined with silymarin for 2 weeks for canine giardiasis. In addition, to observe effects on nutrition, we investigated the changes of body weight, the serum biochemical indicators for liver inflammation (GOT, GPT, NH3), the liver cell regeneration indicators (total protein, albumin) and the hematological changes during treatment (WBC, RBC, MCV, MCH and MCHC). The dogs were allocated to four groups; one group was treated with silymarin (3.5 mg/kg once a day, oral), another with metronidazole (50 mg/kg once a day, oral), and the other group with silymarin (3.5 mg/kg once a day, oral) plus metronidazole (50 mg/kg once a day, oral), while control group remained nontreated. The fecal samples from all the dogs were examined, using the ZSCT and giardia antigen test kit (SNAP(*) Giardia, IDEXX Laboratories), from each dog of each group for three times a week for 2 weeks. Dogs were considered to have giardiasis when one or more of the fecal samples had positive results for Giardia cysts. Seven days after treatment, the efficacy of silymarin plus metronidazole was found 79%, whereas that of metronidazole was 72%. Ten days post-treatment the efficacy of metronidazole plus silymarin (91%) was significantly different in comparison with that of metronidazole (75%). Two weeks post-treatment no cysts were detected in the fecal samples in the dogs of metronidazole or silymarin plus metronidazole-treated groups. Whereas, the fecal samples of all the dogs of the control and only silymarin-treated groups were giardia positive. Signs of side effects were not observed in silymarin plus metronidazole-treated dogs. But poor appetite and intermittent vomiting signs were observed in two dogs of the metronidazole-treated group that resolved when metronidazole administration was discontinued. The body weight of those treated with metronidazole was significantly decreased in comparison with those treated with silymarin and metronidazole plus silymarin. There were significant differences of body weight between the dogs treated with silymarin and metronidazole. Two weeks after metronidazole treatment, serum concentration of GOT, GPT and NH3 were significantly increased in comparison with those treated with silymarin. On the other hand, the serum concentration of GOT, GPT and NH3 were not significantly increased when treated with silymarin plus metronidazole compared to those treated with metronidazole. Serum total protein and albumin concentrations were decreased after metronidazole treatment as compared to those treated with silymarin and silymarin plus metronidazole. The concentrations of serum total protein and albumin decreased significantly in metronidazole-treated group as compared to that of treated with silymarin. The numbers of WBC and RBC did show significant differences in the dogs treated with metronidazole, while MCV, MCH were significant by different between silymarin and metronidazole-treated dogs. On the other hand, there were no significant differences in MCHC in any groups. These data suggest that silymarin, in supplement with antiprotozoal drugs, can influence the therapy of canine giardiasis.