FoxP3 and IDO in Canine Melanocytic Tumors.

Human melanoma is one of the deadliest forms of cancer, with poor prognosis and high resistance to chemotherapy and radiotherapy. The discovery of immunosuppressive mechanisms in the human melanoma microenvironment led to the use of new prognostic markers and to the development of immunotherapies targeting immune checkpoint molecules. Immunoescape mechanisms in canine melanoma have not yet been investigated, and no such immunotherapy has been tested. The aim of this study was to provide preliminary data on the expression of transcription factor forkhead box protein P3 (FoxP3) and indoleamine 2,3-dioxygenase (IDO) in primary canine melanocytic tumors and to investigate their prognostic role. Formalin-fixed, paraffin-embedded samples from 74 canine melanocytic tumors (26 oral melanomas, 23 cutaneous melanomas, and 25 cutaneous melanocytomas) were retrospectively evaluated by immunohistochemistry to explore the expression of FoxP3 and IDO. An increased risk of death due to melanoma was associated with a higher number of FoxP3+ cells per high-power field (FoxP3+/HPF), a higher percentage of CD3+ cells that were also FoxP3+ infiltrating and surrounding the tumor (%FoxP3), and a higher number of IDO+ cells/HPF (IDO+/HPF). A prognostic value for FoxP3 and IDO is suggested by our study, with optimal cutoffs of 14.7 FoxP3+ cells/HPF, 6.1 IDO+ cells/HPF, and 12.5% FoxP3+ cells. Both markers were also associated with tumor type. Multivariable analysis identified IDO+/HPF ( P < .001) as an independent prognostic marker. Even though stratification by diagnosis caused a loss of significance, results from the present study suggest a prognostic role for IDO and FoxP3, possibly related to the establishment of an immunosuppressive microenvironment.

Clinical outcome and cyclo-oxygenase-2 expression in five dogs with solar dermatitis/actinic keratosis treated with firocoxib.

BACKGROUND: The conversion of arachidonic acid into prostaglandin is catalysed by the cyclo-oxygenases (COX-1/COX-2). Several studies indicate that COX-2 is overexpressed in actinic keratosis in humans and dogs. Firocoxib is a COX-2-selective inhibitor that blocks the biochemical activity of COX-2. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of firocoxib (5 mg/kg orally once daily) for the treatment of dogs with solar dermatitis/actinic keratosis. METHODS: Firocoxib 5 mg/kg was given orally once daily for 180 days to five dogs with clinical signs and histopathological lesions consistent with solar dermatitis/actinic keratosis. On days 0, 50 and 180, the severity of erythema, skin shine, induration and the number of comedones were evaluated by a clinical scoring system. On the same days, samples were collected for histopathology from 'target lesions' and COX-2 expression was evaluated by immunohistochemistry. RESULTS: The clinical follow-up showed that four of five dogs improved with the treatment; improvement in terms of histological findings was correlated with the regularization of the epidermal proliferation rather than the recovery of dermal changes. CONCLUSIONS AND CLINICAL IMPORTANCE: A role for COX-2 might thus be hypothesized in the pathogenesis of canine solar dermatitis.

Tumours in European Shorthair cats: a retrospective study of 680 cases.

OBJECTIVES: Naturally occurring tumours in domestic cats are less common than in dogs and represent the leading cause of death among older animals. The main objective of this study was to analyse a large data set of histologically diagnosed tumours to highlight the most common World Health Organization (WHO) tumour histotypes, the effect of age and sex, and the International Classification of Diseases for Oncology (ICD-O) topographical site predilections of feline breed-specific tumours. METHODS: A total of 680 feline tumours diagnosed in European Shorthair cats by three veterinary diagnostic laboratories located in central Italy from 2013 to 2019 were collected. Data on age, sex and topography of lesions were recorded. Samples were morphologically and topographically coded using the WHO and the ICD-O-3 classification system. RESULTS: Skin and soft tissue neoplasms comprised 55.9% of all tumours, followed by mammary gland (11%), alimentary tract (7.9%), oral cavity and tongue (7.3%), nasal cavity and middle ear (6%), lymph node (3.1%), bone (1.8%) and liver/intrahepatic bile duct (1.3%) tumours. Squamous cell carcinoma (SCC), sarcoma, lymphoma and basal cell tumours were the most diagnosed neoplasms. Malignant tumours were 82.9% of the total and the topographical sites mainly involved were skin (C44), connective/subcutaneous/other soft tissues (C49), mammary gland (C50), small intestine (C17), nasal cavity and middle ear (C30), and gum (C03). CONCLUSIONS AND RELEVANCE: This study aimed to provide an in-depth evaluation of spontaneous feline tumours in the European Shorthair cat breed. Results identify SCC as the most commonly represented skin neoplasm. It is likely that the analysed feline population, living in southern latitudes, was more subject to prolonged exposure to ultraviolet light, explaining the discrepancy with previous studies in which SCC was less represented.