Evaluation of COX-2 Expression in Canine Mammary Tumors and Its Relation to NSAID Therapy

Abstract

Canine mammary neoplasia is considered as an excellent naturally occurring animal tumor model for human breast cancer. Nearly half or more of the canine mammary neoplasms are malignant, overexpress COX-2 and show poor prognosis, particularly those having inflammation. Therefore, the use of anti-inflammatory drugs such as NSAIDs has recently been considered useful in prolonging the life span and in palliative care of human mammary cancer patients. However, there seems to be scarcity of information on the role of NSAIDS in canine mammary tumor. The present study was conducted with a view to evaluate COX-2 expression in canine mammary tumor and its relation to NSAID therapy. For this purpose, 42 dogs (40 females, 2 males) were included in this study with an average age of affected dogs 9.17 years (range, 4-15 years). Among these 28 had primary tumor at examination and 15 had relapsed neoplasm. (One dog had both primary and relapsed tumor). COX-2 immunohistochemical staining was scored independently and in a blinded manner by two investigators from 1728 tissue array cores stained by LSAB method. The histopathology revealed that there were 13 benign (30,95%) and 29 malignant (69,05%) mammary tumours. Out of the latter, 15 were simple carcinomas, 8 complex carcinomas, 1 carcinosarcoma and the rest sarcomas. When graded 14, 7 and 8 belonged to the grade 1, 2 and 3 respectively. The COX-2 expression was elevated, in general, in malignant mammary tumors as compared to benign counterparts and more so in sarcomas and the staining intensity was significantly higher in both carcinoma and the sarcoma sub-types as compared to the benign tumors. The survival of the animals with different types of tumors was significantly higher in benign tumors than in malignant ones (carcinoma complex and sarcoma sub-types), and the relapse free period was also higher in benign lesions compared to the simple carcinomas and the sarcomas. Those patients which had higher COX-2 percent than 50%, showed markedly lower survival time than those with COX-2 percent lower than 50%. The patients with NSAID therapy did not show an increase in survival time neither in malignant tumours, nor in carcinomas although, the patients in which the tumour COX-2 percent was higher than 50% lived significantly longer when treated with NSAID therapy. In a nutshell, COX-2 expression of mammary gland tumors negatively correlated with the survival time and the relapse, but positively correlated with the tumor volume. The patients who recieved firocoxib showed significantly higher survival than those who did not receive NSAIDs, or received other NSAID than firocoxib viz.piroxicam and meloxicam.