Squamous cell carcinoma is the most common ocular neoplasm and the second most common tumor overall in horses.1 Common sites of predilection for SCC in horses include the squamous epithelium of the head, eye, ocular adnexa, and genitalia. The etiology of the disease is incompletely understood, but suggested predisposing factors include exposure to solar radiation and certain viruses, absence of pigmentation, chronic physical irritation, and hormonal or immunologic influences.2 Draft breeds (eg, Belgians and Clydesdales), Paint Horses, and Appaloosas have a higher prevalence of SCC than other breeds.3 Although SCC rarely metastasizes to remote sites, the tumor is locally invasive. As a result of its local effects, ocular SCC tends to cause destruction of the globe and blindness. Treatment options are numerous and include surgical excision, cryotherapy, radiofrequency hyperthermia, immunotherapy, radiation therapy, laser surgery, intralesional chemotherapy, or a combination of those modalities.2,4 Treatment options for ocular and adnexal SCC vary depending on location of tumor, depth and size of tumor, the horse's use, presence or absence of metastatic disease, equipment availability, and financial constraints.4 Unfortunately, recurrence has been reported as a complication of all presently available treatment methods.5–12
Cyclooxygenases are a family of enzymes responsible for conversion of arachidonic acid to prostaglandins.13 Multiple isoforms of COX exist, with COX-1 and COX-2 being the most biologically active. Although these isoforms have similar enzymatic activity, they are expressed by separate genes and differ in physiologic function. Traditionally, COX-1 has been described as being expressed constitutively in healthy tissues and as being active in numerous homeostatic functions, including gastrointestinal tract cytoprotection, maintenance of platelet function, and maintenance of renal blood flow. In contrast, COX-2 has been described as an inducible enzyme that is overexpressed in inflammatory and neoplastic conditions via signals such as cytokines, hormones, and tumor promoters. However, the simplified paradigm of COX-1 being constitutive and associated with physiologic homeostasis and COX-2 being inducible and associated with pathologic conditions has not been upheld by research. It is now known that COX-2 often plays a critical physiologic role and is constitutively expressed in many tissues, including the kidneys, pancreas, stomach, colon, uterus, and eyes.14–23
High levels of COX-2 expression have been detected in human and veterinary neoplasms, including colorectal cancer,24 breast cancer,25 hepatocellular carcinoma,26 and SCC of the head and neck27 in humans and epithelial neoplasias such as nasal epithelial SCC, nasal carcinoma, renal cell carcinoma,28 transitional cell carcinoma,29 and nasal adenocarcinoma30 in dogs. Correlations have been made in humans with SCC involving the head and neck between overexpression of COX-2 in neoplastic tissues and poor prognostic factors (eg, enhanced tumor vascularization and increased likelihood of metastasis).27 Mechanisms responsible for such changes are being investigated. Correlations have been found between COX-2 overexpression, prostaglandin E2 concentration, vascular endothelial growth factor (a potent angiogenic factor) concentration, and angiogenesis in SCC of the head and neck in humans, suggesting that there are inducible relationships among these factors.27
To the authors' knowledge, investigation of the role of COX in naturally occurring equine ocular and periocular SCC has not been reported. The objective of the present study was to determine whether COX is overexpressed in SCC-affected ophthalmic tissues in horses.
Squamous cell carcinoma
Surgipath X-tra slides, Surgipath Medical Industries Inc, Richmond, Ill.
Black and Decker HS2000 vegetable steamer, The Black and Decker Corp, Towson, Md.
Dako target retrieval solution S1699, Dako, Glostrup, Denmark.
Tris with tween buffer, Dako, Glostrup, Denmark.
A/B block, Vector Laboratories, Burlingame, Calif.
Protein block X0909, Dako, Glostrup, Denmark.
Goat polyclonal anti-human cyclooxygenase 1, Santa Cruz Biotechnology Inc, Santa Cruz, Calif.
Rabbit polyclonal anti-C terminal peptide of murine cyclooxygenase-2, Cayman Chemical, Ann Arbor, Mich.
DAB K3466, Dako, Glostrup, Denmark.
Olympus BX 60 microscope, Olympus, Center Valley, Penn.
SPOT Insight digital camera, SPOT Diagnostic Instruments, Sterling Heights, Mich.
ImagePro software, Media Cybernetics, Silver Springs, Md.
Microsoft Excel, Microsoft Corp, Redmond, Wash.
Systat Software Inc, Point Richmond, Calif.
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Summary of signalment data for 20 horses evaluated in a study of SCC of ocular adnexal tissues.
|Breed||Age (y)||Sex||Tissue site|
|Tennessee Walking Horse||16||Mare||SCC-eyelid|
|American Paint Horse||10||Mare||SCC-eyelid|
|American Paint Horse (overo coat pattern)||4||Gelding||SCC-third eyelid|
|American Saddlebred||3||Mare||SCC-third eyelid|
|American Paint Horse||5||Gelding||SCC-third eyelid|
|Tennessee Walking Horse||27||Mare||Control|
|American Paint Horse||6||Mare||Control|