Dados do Trabalho

Título

HER-2 immunohistochemical analysis in feline bone tumors: preliminary evaluation and expression differences from human bone tumors and its animal model.

Introdução

Bone tumors (BT) are rare in cats, but osteosarcoma (OSA) still figures as the most frequent one. Compared to human OSA and its animal model, the dog, feline OSA is less aggressive, with low metastasis rate (5-10%), possibly due to a distinct molecular profile. HER-2 (C-erbB-2) is a glycoprotein with tyrosine kinase activity and growth factor function. Its overexpression leads to malignant tumor progression in man and dog. HER-2 expression in feline BT is unknown.

Objetivo

To evaluate HER-2 immunohistochemical (IHC) expression in feline BT and its prognostic implications. Identifying differences between species can help understand feline BT favorable biological behavior and distinct molecular expression pattern when compared to canine and human BT.

Métodos

Study approved by UFF Ethics Committee in Animal Use (protocol 7046100123). Six formalin-fixed-paraffin-embedded samples from feline BT were selected and revised from UFF Veterinary Pathological Anatomy Laboratory archives. IHC analysis for anti-cerb-B2 antibody (1:150µL; clone Y1248, Dako) was performed by streptavidin-biotin-peroxidase method. Diaminobenzidine (DAB) was the revelation system, counterstained with Harris hematoxylin. Positive and negative controls were included according to manufacturer. Samples were evaluated in semi-quantitative scale, the score used to classify each sample labeling graded from zero (0) to three (3+), according to immunostained cell proportion, considering cytoplasmatic as well as membrane staining. Immunomarking intensity was not considered for grading. The highest positivity grade observed in any sample area was recorded as HER-2 final score. Results were evaluated by descriptive statistical tools.

Resultados

From six feline BT samples, four cases were OSA and two cases chondrosarcoma (CSA). As in dogs and man, OSA was the most frequent BT. OSA were osteoblastic (ob; 1), chondroblastic (ch; 2) and fibroblastic (fib; 1). OSA subtypes are also described in human and canine OSA, though its prognostic value remains uncertain. Five cats were male and one female, all of no specific breed. Males are slightly more affected by human and canine BT. More cases are needed is order to prove it in cats. Age average from five cats (one not informed) was 8,4 years old, varying from 4 to 14 years old. Similar to canine, BT is an elderly feline disease. Both CSA and fib OSA affected femur. Ob OSA was located on thoracic limb (no specific bone informed). Ch OSA affected scapula and rib, the single axial OSA case. Appendicular BT, specially OSA, is more frequent than axial location in man and its canine animal model. Only ob OSA and fib OSA scored HER-2 2+ (33,33%). All other BT were HER-2 1+ (66,67%). Despite small sample number, over 50% of feline BT were considered negative for HER-2 expression, differing from human BT. This feature can be related to feline BT slow tumor progression and low metastasis rate.

Conclusões

Feline BT IHC differences, such as in HER-2 score, can help understanding tumor progression, low metastatic rates and slow metastasis development in cats. Such studies may provide molecular insights in protein expression that could contribute to a more efficient disease control in human BT, despite dogs being considered the classical animal model for spontaneous bone tumors, mostly OSA.

Palavras-chave

bone tumor, HER-2 expression, animal model differences

Financiador do resumo

This study was funded/financed in part by PROPPI UFF - Pró-reitoria de Pesquisa, Pós-Graduação e Inovação da Universidade Federal Fluminense, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and FAPERJ—Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro.