Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma.

Canine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow-up of 6 months. Epidemiological, clinical and histological data were collected and quantitative-PCR were performed on formalin-fixed paraffin-embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor.

Feline progressive histiocytosis: a retrospective investigation of 26 cases and preliminary study of Ki67 as a prognostic marker.

Feline progressive histiocytosis (FPH) is an uncommon and infrequently reported cutaneous histiocytic proliferative disorder, whose clinical presentation is solitary or multiple cutaneous nodules and papules, with late-course internal metastasis. We describe herein the clinical, epidemiologic, histologic, and immunohistochemical features of this entity, and document the outcome of FPH based on a retrospective study of 26 cases. Female and male cats were affected equally. Lesions were evident either as solitary (16 of 26 cases) or multiple (10 of 26 cases) nonpruritic and alopecic nodules or plaques, preferentially located on the legs and extremities (73%). Follow-up was complete for 19 cats, and ranged from 41 to 1,449 d. Nine died of FPH with a median overall survival of 96 d (range: 41-238 d). The disease recurred in 14 cats after surgical excision of the nodules, and the median disease-free survival was 175 d (range: 21-1,449 d). Five of the 26 cats were alive at the end of the study, and 4 had no progression of the disease. Histologically, lesions were characterized by poorly circumscribed, unencapsulated histiocytic infiltration of dermis and subcutis. Epitheliotropism was observed in 11 (42%) cats. Atypical histiocytes diffusely and consistently expressed MHC II, CD18, and Iba1. Statistically significant higher E-cadherin expression was observed in epitheliotropic cases compared to non-epitheliotropic cases. A negative correlation between overall survival and proliferation index was evident, thus suggesting Ki67 as a promising prognostic marker.

Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways.

A KIT-positive gastrointestinal stromal tumor in a ferret (Mustela putorius furo).

A 1.5-year-old, neutered, male ferret (Mustela putorius furo) was presented with sudden lethargy, anorexia, and diarrhea. Clinical and radiographic examinations revealed an intra-abdominal mass. An explorative laparotomy was performed. A neoplasm, located in the ileum wall, was submitted for histopathologic examination. The tumor consisted of weakly eosinophilic spindle cells arranged in a compact pattern with haphazardly interlacing bundles. Neoplastic cells labeled positively for KIT (cluster of differentiation 117, stem cell factor receptor) and vimentin. Based on histologic and immunohistologic results, this tumor was diagnosed as a gastrointestinal stromal tumor. Results suggest that this ferret tumor shares strong similarities with the canine and human counterparts.

Apoptosis and anti-apoptotic heat shock proteins in canine cutaneous infundibular keratinizing acanthomas and squamous cell carcinomas.

Cell stress and death are linked in the neoplastic process, and heat shock proteins appear to play an important role by inhibiting apoptotic pathways. The apoptotic rates in 9 canine infundibular keratinizing acanthomas (IKAs) and 17 canine squamous cell carcinomas (SCCs) were correlated with the immunohistochemical expression of caspase-3 and the antiapoptotic heat shock proteins Hsp27, 72 and 73. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) method. The absence of a correlation between the TUNEL index and active-caspase-3 expression, a paucity of active-caspase-3-positive cells and Hsp72 over-expression were considered to be indicative of inhibition of apoptosis, and suggestive that inhibition of cell death plays a key role in oncogenesis and tumour growth of some canine skin neoplasms.