COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic fmolecular markers

Abstract

Cyclooxygenase (COX)-2 is an inducible enzyme linked to tumor growth and angiogenesis. Its expression occurs in a wide range of preneoplastic and neoplastic conditions in humans, including colon and breast carcinomas. We evaluated the role of COX-2 as a mediator of angiogenesis in feline and canine invasive carcinomas (IMCs) and its role as a prognostic indicator. COX-2 expression was assessed in neoplastic samples and healthy mammary glands by immunohistochemistry, and related to the following clinicopathological parameters: age, tumor size, histologic type, tumor grading, vessel invasion, estrogen (ER) and progesterone receptor (PR) status, Ki-67, HER-2 overexpression, microvessel density (MVD), VEGF expression and overall survival (OS). In both species, COX-2 immunoreactivity was not observed in healthy tissues, whereas 96% of feline and 100% of canine invasive carcinomas scored positive. In queens, COX-2 overexpression was significantly correlated to ER-negative status (p=0.04) and to increased PR (p=0.038) expression, and angiogenesis assessed by VEGF expression (p=0.002). In bitches an increased COX-2 expression was significantly correlated to HER-2 overexpression (p=0.013) and to tumor dedifferentiation (p=0.03). In both species increased levels of COX-2 were correlated to poorer prognosis (p=0.03 in dogs and p=0.002 in cats). COX-2 is expressed in mammary tissues during tumorigenesis and its expression is associated with a poorer prognosis in bitches and queens. The correlation of COX-2 expression and angiogenesis provides support for a potential role of COX-2 inhibitors for the prevention and the treatment of feline IMCs via their anti-angiogenic properties. In the canine species, moreover, COX-2 may be important for mediating HER-2 induced mammary tumors.

Cyclooxygenase-2 Expression in Equine Tumors

“…This is in contrast to what is reported in the veterinary literature, in which COX-2 expression is more often upregulated in metastases and/ or associated with a worse outcome after therapy. 3,7 Based on the data provided in this study, COX-2 appears to be expressed in very few equine sarcoids, a substantial number of melanomas, and the large majority of SCC. Most SCC demonstrated poor-tomoderate immunoreactivity, and immunoreactivity was independent of anatomic site.…”

“…10,11 Recent studies demonstrated COX-2 expression in a variety of canine carcinomas, including urinary bladder and mammary gland, as well as squamous-cell carcinoma (SCC), melanoma, and osteosarcoma. 3,5,7 COX-2 expression has been demonstrated in feline mammary carcinoma and in a subset of feline transitional-cell carcinomas and SCC. 1,3 Furthermore, strong COX-2 expression may confer a worse prognosis in canine and feline mammary tumors and canine osteosarcoma.…”

“…3,5,7 COX-2 expression has been demonstrated in feline mammary carcinoma and in a subset of feline transitional-cell carcinomas and SCC. 1,3 Furthermore, strong COX-2 expression may confer a worse prognosis in canine and feline mammary tumors and canine osteosarcoma. 3,7 There is accumulating epidemiologic and clinical evidence that inhibition of COX-2 with nonsteroidal anti-inflammatory drugs (NSAID) may reduce the occurrence of cancer in humans.…”

“…1,3 Furthermore, strong COX-2 expression may confer a worse prognosis in canine and feline mammary tumors and canine osteosarcoma. 3,7 There is accumulating epidemiologic and clinical evidence that inhibition of COX-2 with nonsteroidal anti-inflammatory drugs (NSAID) may reduce the occurrence of cancer in humans. 10,11 Furthermore, the NSAID piroxicam has been shown to induce meaningful antitumor responses in dogs with certain malignancies, such as transitional-cell carcinoma and oral SCC.…”

ISFM and AAFP Consensus Guidelines: Long-Term use of NSAIDs in Cats

“…44 The expression of COX-2 may also be upregulated in certain neoplasms, and in cats variable expression has been reported in transitional cell carcinomas, squamous cell carcinomas, mammary carcinomas and pancreatic carcinomas. [25][26][27][28][45][46][47] However, just as COX-2 has some constitutive expression, COX-1 expression also has a role to play in the inflammatory response. 39,40 COX and LOX selectivity, and NSAID adverse effects Inhibition of COX-1, the enzyme predominantly associated with homeostatic functions, is reported to be the cause of most NSAID-induced side effects such as gastric ulcers and blood dyscrasias.…”