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.

中文翻译：

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Cyclooxygenase-2 表达与口腔和皮肤犬黑色素瘤中炎症细胞的浸润有关。


黑色素瘤是狗体内生长快速的肿瘤，占皮肤恶性肿瘤总数的 7%，也是口腔中最常见的肿瘤。在这些肿瘤中，环氧合酶-2 (COX-2) 的高表达与不良预后相关。本研究的目的是验证COX-2的过度表达是否与淋巴细胞的调节有关，以及是否与黑色素瘤的血管生成和增殖能力有关。采用免疫组织化学方法对犬黑色素瘤样本（n = 85）进行分析，检测 S-100、Melan-A、PNL-2、COX-2、因子 VIII、Ki-67 和免疫细胞标志物（CD3、CD4、FOXP3 和MAC387）；免疫荧光法测定MAC387、NOS、CD206的表达水平。我们的研究显示 COX-2 表达和炎症细胞浸润之间存在并发差异：口腔黑色素瘤在 34% 的病例中显示 COX-2 阳性，并且这种表达与炎症浸润和血管生成中 CD3 阳性相关；而皮肤黑色素瘤在 42% 的病例中呈现 COX-2 阳性，并且这种表达与 CD3、CD4、FOXP3 和 MAC387 的阳性染色相关。这些标记物与炎症细胞、血管生成和增殖相关。有趣的是，黑色素瘤被 FOXP3+ 细胞高度浸润，这与血管生成有关，而 CD3、CD4 和 MAC387 表达仅与皮肤黑色素瘤相关。巨噬细胞谱分析表明，COX-2 低表达的口腔和皮肤黑色素瘤均具有 M1 表型，而 COX-2 高表达的病例则表现出混合的 M1/M2 谱模式。 我们的结论是，COX-2 在 42% 的皮肤黑色素瘤和 34% 的口腔黑色素瘤中过度表达，与血管生成、增殖和瘤内淋巴细胞浸润直接相关。我们认为 COX-2 是免疫细胞浸润的关键调节因子，可能驱动肿瘤相关巨噬细胞激活。