惡性黑色素瘤患犬COX-2在不同解剖位置的表現與預後之相關

Abstract

惡性黑色素瘤（MM）具有局部侵犯特性並伴隨高遠端轉移率和較短的存活時間，管理此疾病上仍充滿挑戰。近期有文獻指出，使用與腫瘤進展相關的環氧合酶-2（COX-2）作為治療標的，例如以非類固醇類消炎藥（NSAIDs）來治療惡性黑色素瘤。先前的研究顯示其中一種NSAIDs即piroxicam，對於特定腫瘤如移形上皮細胞癌具有抗腫瘤活性。本研究的目的為探討(1)惡性黑色素瘤在不同解剖位置（口腔內但非舌頭、舌頭、腳趾）之COX-2表現，與(2)在接受piroxicam治療的患犬中COX-2表現與總存活時間（OST）的關聯，並進一步比較其與臨床和病理型態學因子之相關性。OST定義為發現腫瘤至病犬死亡之間期。此篇回溯型研究共收集84隻經組織病理學確診為惡性黑素瘤的患犬。COX-2的表現以免疫組織化學法來測定並評估免疫反應分級、強度和反應程度分數。單變因分析顯示COX-2表現與OST沒有顯著相關性，但腫瘤位置則顯著影響OST（P<0.05）。在48隻接受piroxicam治療的患犬分組中，COX-2的反應程度分數和強度僅於單變因分析結果發現與OST顯著相關（P<0.05）。多變因分析結果顯示piroxicam治療 分組中有接受手術切除、原發於腳趾位置、發現腫瘤時間至確診時間較久的患犬之OST較長（P <0.05）。此篇研究發現COX-2表現量與犬惡性黑色素瘤的腫瘤發生位置無關，但在piroxicam治療的患犬若COX-2表現較高則有較好的預後。因此，COX-2表現量可能作為惡性黑色素瘤患犬在接受piroxicam輔助治療的指標。

Malignant melanomas (MM) are locally aggressive and associated with high metastatic potential and shorter survival time, which remained a challenge to management. Cyclooxygenase-2 (COX-2), which is thought to involve in the tumor progression, has recently been suggested as a therapeutic target such as nonsteroidal anti-inflammatory drugs (NSAIDs) in MM. Previous reports have demonstrated that piroxicam, one of NSAIDs, has an antitumor activity on certain tumors such as transitional cell carcinoma. The aims of this study were to investigate (1) the COX-2 expression of MM at different locations (non-lingual oral, tongue and digital location), and (2) the correlation between COX-2 expression and the overall survival time (OST) of dogs that had piroxicam, and further comparing with the related clinico-morphological factors. The OST is defined from tumor first noted to death. This retrospective study enrolled 84 dogs that were diagnosed as malignant melanoma histopathologically. The COX-2 expression was determined immunohistochemically for the evaluation of immunoreactivity grade, intensity, and reactivity score. The univariate analysis revealed that COX-2 expression had no significant impact on OST. However, tumor location had significantly associated with OST (P < 0.05). Of 48 dogs in the piroxicam-treated group, COX-2 score and intensity were significant related to OST (P < 0.05) in univariate analysis but not in multivariate analysis. Results of multivariate analysis revealed that surgical removal, digital location, and the long time between observation to diagnosis were positively associated with OST (P < 0.05) in the piroxicam-treated group. This study demonstrated that COX-2 expression level was not associated with tumor locations, and piroxicam-treated group with high COX-2 expression had better outcomes. In conclusion, the COX-2 expression level may be used as an indicator for piroxicam adjuvant therapy in dogs with MM.