Dados do Trabalho

Título

Canine squamous cell carcinoma: PCNA immunoexpression evaluation and anatomical tumor location in an animal model

Introdução

Neoplasms are a major cause of death in dogs and humans. Cutaneous tumors (CT) comprises 30% of all diagnosed tumors in dogs. Squamous cell carcinoma (SCC) represents about 15% of CT in dogs and 20% in humans. Proliferating Cell Nuclear Antigen (PCNA) is a protein that functions in damaged DNA molecule repair. Its high expression in cancer is associated with increased cell proliferation rates and advanced stages of malignancy. The dog can be an experimental model for translational studies in human CT.

Objetivo

To evaluate PCNA immunohistochemical (IHC) expression in SCC in dogs as an animal model of spontaneous CT. Preclinical studies with drugs that inhibit canine cell proliferation can be translationed to metastatic and unresectable CT in humans.

Métodos

Study approved by UFF Ethics Committee in Animal Use (protocol 4900150721). Histopathological analysis of 10 canine cutaneous nodules was revised from UFF Veterinary Pathological Anatomy Laboratory (LAPV-UFF) archives. IHC analysis for anti-PCNA antibody (clone PC10, dilution 1:700 μl, Dako) was performed by streptavidin-biotin-peroxidase method. Diaminobenzidine (DAB) was the revelation system, counterstained with Harris hematoxylin. Positive control was included according to manufacturer. Primary antibody was replaced by the same Ig isotype as negative control. Nuclear immunolabeling was evaluated under optical microscopy, in 15 high power fields. Only cells with strong dark brown nuclear staining were considered positive. Positivity percentual was calculated based on immunopositive cells average, according to each neoplasm type. Results were evaluated by descriptive statistical tools.

Resultados

Five nodules (50%) were well differentiated SCC (WD SCC), 4 (40%) moderately differentiated SCC (MD SCC) and 1 (10%) poorly differentiated SCC (PD SCC). There were six female and four male dogs, with age average of 8 years, from Dogo Argentino, Rottweiler, Dachshund, German Shepherd, Yorkshire Terrier (10%, 1/10 each), Pitbull (20%, 2/10) breeds and mongrels (30%, 3/10). Ear was the most affected site in this study (30%, 3/10), followed by head and digit (20%, 2/10 each), neck, perianal region and back, representing 10% (1/10) each. Dogs with brown coat color were the majority of cases (40%, 4/10), followed by black/brown and white/brown coat colors, with 30% (3/10) each. All SCC showed positive staining for PCNA. WD SCC showed positive immunomarking PCNA average of 59.32%, while MD SCC was 59.91% and PD SCC presented 66.38% of PCNA-positive cells.

Conclusões

Of the evaluated dogs, the most affected body locations were those most exposed to sun light, even in dogs with dark fur, similar to humans, due to sun exposure. High age average of studied dogs is similar to what is described in humans with SCC. WD and MD SCC showed a higher average of PCNA immunostaining than the single PD SCC, suggesting cell proliferative mechanisms preservation, being better targets for chemotherapy than PD SCC. Studies with a larger number of samples are needed to elucidate this assumption.

Palavras-chave

squamous cell carcinoma; proliferating cell nuclear antigen; canine animal model

Financiador do resumo

This study was funded/financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and FAPERJ—Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro.