COX-2 expression is associated with infiltration of inflammatory cells in oral and skin canine melanomas

T L Silveira, E S Veloso, I N N Gonçalves, R F Costa, M A Rodrigues, G D Cassali, H L Delpuerto, Lisa Pang, David Argyle, E Ferreira

Research output: Contribution to journalArticlepeer-review

Abstract

Melanoma is a fast-growing tumor in dogs and represents 7% of the total malignant neoplasms from the skin and is the most common tumor found in the oral cavity. In these tumors high expression of 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 analyzed 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 overxpressed 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 tumor associated macrophage activation. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalVeterinary and Comparative Oncology
Early online date23 Apr 2020
DOIs
Publication statusE-pub ahead of print - 23 Apr 2020

Keywords

  • COX-2
  • canine melanoma
  • inflammation
  • macrophages
  • immunohistochemistry
  • DOG

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