P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are major actors in multidrug resistance (MDR) phenomenon in both human and canine mammary carcinomas (CMCs). The aim of this study was to investigate an association between the intrinsic expression of P-gp and BCRP compared to the immunophenotypes and outcome in CMCs. Fifty CMCs were evaluated at immunohistochemistry (IHC) for P-gp, BCRP, Estrogen receptor alpha (ER), Progesterone receptors (PR), Human Epidermal Growth Factor Receptor type 2 (HER2), basal cytokeratins 5/6 (CK5/6), Epidermal Growth Factor Receptor 1 (EGFR), and Ki67 proliferation index. P-gp and BCRP positive cases were, respectively, 52% and 74.5%, with a significantly higher expression of BCRP than P-gp. Five immunophenotypes were defined in 37 out of 50 CMCs: 9 (24.3%) Luminal A, 5 (13.5%) Luminal B, 9 (24.3%) HER2 overexpressing, 9 (24.3%) Triple-negative basal-like, and 5 (13.5%) Triple-negative non-basal-like. In all CMCs at least one marker was expressed. Follow-up data were available for 25 animals. The average cancer-specific survival was 739 ± 444 days. A number of CMCs bear a high expression of P-gp and BCRP but no significant association was found between their expression and the immunophenotypes, Ki67 index, the histological grade, and tumor-related death.
A retrospective study was performed to establish the causes of mortality and incidence patterns of tumors in young (<50 weeks) control CD-1® mice from Charles River Laboratories. Tumor incidences (fatal and nonfatal) and nonneoplastic causes of death observed during the first 50 weeks of the study were collected from 48 thirteen-week toxicity studies conducted between 2009 and 2018 and from 43 carcinogenicity studies conducted between 2005 and 2018. Thirteen-week studies had a mortality rate of 8/620 (1.3%) in males and 4/620 (0.65%) in females. The major factors contributing to death were integument lesions in males (3/8) and experimental procedure–related injuries in females (3/4). All tumors recorded were nonfatal. Bronchiolo-alveolar adenoma was the commonest tumor with the same incidence in both males and females (4/620, 0.65%); a single lymphoma (0.16%) and uterine leiomyosarcoma (1/620 0.16%) were reported in females. The mortality rates of males and females that died or were euthanized during the first 50 weeks in carcinogenicity studies were 192/2830 (6.8%) and 198/2830 (7%), respectively. The most common fatal tumor in this age group was lymphoma in both sexes, with an incidence of 18/192 (9.3%) and 41/198 (20.7%) in males and females, respectively. In males tumors were responsible for fewer deaths than in females (17% vs. 32.3%). The major nonneoplastic causes of death or moribundity were cutaneous lesions (44/192, 22.9%), and obstructive uropathy (39/192, 20.3%) in males, and chronic progressive nephropathy (40/198, 20.2%) in females. Only minor differences were evident compared to a similar study performed 15 years ago; these might reflect changes in terminology and diagnostic criteria, and stricter animal welfare endpoints.
Idiopathic pericarditis (IP) and pericardial mesothelioma (PM) are causes of pericardial effusion in dogs. Pericardiectomy can be a definitive treatment in the case of idiopathic pericardial effusion or a short-term intervention for mesothelioma. The aim of the present study was to investigate which histopathologic parameters are correlated with clinical outcomes in a cohort of dogs that underwent pericardiectomy. The histopathological findings of 22 IPs and 5 PMs were compared with clinical and survival data and the immunohistochemical characterization of immune cells (CD3, CD79α, Iba1). In IP, the mesothelium was lost in 20 cases, reactive in 9, atypical in 3, and mesothelial papillary hyperplasia (MPH) was observed in 4 cases. Numerous macrophages were found in both IPs and PMs especially at the superficial layer of the pericardium. T lymphocytes were observed in mild to moderate numbers and were more numerous than B lymphocytes in both IPs and PMs. MPH was correlated with the quantity of lymphoplasmacytic infiltrate in the superficial layer, inversely related to the thickness of the pericardium, and associated with a longer overall survival. Pericardial fibrosis was present in 19 out of 22 IPs and in all mesotheliomas and was correlated with increased time from initial presentation and pericardiectomy and lymphoplasmacytic infiltrate in the deep zone. Pericardial thickness was correlated with the amount of lymphoplasmacytic and macrophagic infiltrate in the deep zone. Mesothelioma was associated with an increased number of pericardiocentesis procedures before pericardiectomy and with the presence of macrophages in the superficial pericardial layer, edema, fibrin, and hemorrhage. Disease-free interval and overall survival were significantly shorter in patients with mesothelioma compared with IP.
This brief communication details the clinical, macroscopic, histological, and immunohistochemical features of a spontaneous case of uveodermatologic syndrome (UDS) in a laboratory beagle dog. A bilateral and symmetrical panuveitis, rich in macrophages and T lymphocytes, with distinctive extracellular clumped or phagocytised melanin pigment granules, and Dalen-Fuchs nodules was diagnosed following occurrence of ocular symptoms and subsequent blindness in a female peripubertal 9.5-month-old beagle dog. Although no macroscopic lesions were visible in the skin, microscopic examination revealed a histiocytic and lymphocytic lichenoid dermatitis with pigmentary incontinence. UDS has not been described as a background finding in laboratory beagle dogs before, although it is a well-known immune-mediated disease in certain canine breeds. Knowledge that UDS can occur in laboratory beagle dogs involved in preclinical studies, especially ocular studies, is essential for toxicologic pathologists.