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Peer-reviewed veterinary case report

COX-2 enzyme linked to immune cells in dog oral and skin melanomas

By Silveira, Tatiany L et al.·Published in Veterinary and comparative oncology·2020·Department of Pathology, Brazil·View original on PubMed

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Original publication title: Cyclooxygenase-2 expression is associated with infiltration of inflammatory cells in oral and skin canine melanomas.

Species:
dog

Plain-English summary

A study found that 42% of skin melanomas and 34% of oral melanomas in dogs showed high levels of a protein called COX-2, which is linked to a worse outcome. These tumors were also associated with the presence of certain immune cells that can affect tumor growth and blood vessel formation. This suggests that COX-2 may play a significant role in how the immune system interacts with these tumors. Understanding this relationship could help veterinarians develop better treatment strategies for dogs with melanoma.

People also search for: dog melanoma treatment · skin tumor in dogs · oral tumor in dogs · COX-2 in canine cancer · dog cancer prognosis

Abstract

Melanoma is a fast-growing tumour in dogs and represents 7% of the total malignant neoplasms from the skin and is the most common tumour found in the oral cavity. In these tumours, high expression of cyclooxygenase-2 (COX-2) is associated with a poor prognosis. The aim of this study was to verify if the overexpression of COX-2 is related to the modulation of lymphocytes and if it is associated with the angiogenic and proliferative capacity of the melanoma. Canine melanoma samples (n = 85) were analysed by immunohistochemistry to detect the expression of S-100, Melan-A, PNL-2, COX-2, Factor VIII, Ki-67 and immune cells markers (CD3, CD4, FOXP3 and MAC387); and expression levels of MAC387, NOS and CD206 were determined by immunofluorescence. Our study showed a concurrent difference between the expression of COX-2 and inflammatory cell infiltration: Oral melanomas showed positivity for COX-2 in 34% of the cases and this expression was associated with CD3 positivity in the inflammatory infiltrate and angiogenesis; whereas cutaneous melanomas presented positivity for COX-2 in 42% of the cases and this expression was associated with positive staining for CD3, CD4, FOXP3 and MAC387. These markers are associated with inflammatory cells, angiogenesis and proliferation. Interestingly, melanomas were highly infiltrated by FOXP3+ cells, this is related to angiogenesis, whereas CD3, CD4 and MAC387 expression was only associated with cutaneous melanomas. The macrophage profile analysis showed that both oral and cutaneous melanomas with low COX-2 expression have an M1 phenoptype, whereas the cases with high COX-2 expression demonstrate a hybrid M1/M2 profile pattern. We concluded that the COX-2 is overexpressed in 42% of cutaneous melanomas and in 34% of oral melanomas, with a direct association with angiogenesis, proliferation, and intratumoral lymphocyte infiltration. We propose that COX-2 is a key regulator of immune cell infiltration and may drive tumour associated macrophage activation.

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Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/32323423/