The Harry M. Zweig Memorial Fund for Equine Research

All Immunohistochemical Study of Cyclooxygenase-2
Expression in Squamous Cell Carcinoma of the Equine Cornea

Dr. Kenneth Rassnick

Squamous cell carcinoma is the 2 nd most common tumor occurring in horses. Common locations of this cancer include the skin, genital area and stomach but up to 50% of cases may involve the eye. The cause of squamous cell carcinoma involving the ocular structures in horses is not entirely known. Similar to that occurring in people, the ultraviolet component of sunlight may be the cause of this cancer in some horses. Other factors may include viruses, genetics and compromised immune systems.

When squamous cell carcinoma affects the cornea, there are numerous treatment options including surgical excision, local radiation therapy and cryotherapy (freezing). The treatment modality chosen is determined by the size and location of the tumor, availability of equipment, clinical expertise, and often, cost of treatment. Even if treatment of corneal squamous cell carcinoma is undertaken, therapy fails to be curative for many horses. Following treatment, local recurrence may occur in 15-42% of horses. New therapies are needed to treat some horses with this potentially devastating cancer. In humans, topical agents have been shown to be effective in treating corneal tumors. Topical therapy has several advantages when compared with traditional therapies including (1) treating the entire surface of the eye; (2) simplicity of treatment; (3) reduced patient cost; and (4) reduced patient morbidity.

Cyclooxygenases (COX) are a family of enzymes that degrade polyunsaturated fatty acids from cell membranes. There are two forms of COX. COX-1 is ubiquitous throughout the body and is responsible for normal physiologic functions. COX-2 is induced in response to certain stimuli, such as inflammation and carcinogens, and is responsible for events such as cell growth, development, and progression of cancer. There has been accumulating evidence that COX-2 is overexpressed in many cancers and might be a potential target for therapeutic and preventative strategies. For example, the risk of developing certain tumors, including colon cancer, is lower in people receiving aspirin therapy. Aspirin is a drug that effectively inhibits the COX-2 enzyme. In dogs, bladder tumors and tumors of the mouth may partially or even completely regress when treated with drugs that inhibit COX-2.

The purpose of this study is to determine if COX-2 is overexpressed in squamous cell carcinoma of the cornea in horses. The results of this study will help us determine if topical eye drops that inhibit COX-2 can be used to treat this potentially devastating disease in horses.