Ocular Squamous Cell Carcinoma (SCC)

Ocular squamous cell carcinoma (SCC) is one of the most common types of tumors in horses. After sarcoid, it is the second most frequently diagnosed tumor in horses. SCC most commonly develops in the limbal region (the transitional area between the cornea and sclera) and tends to spread axially into the cornea. It gradually causes visual impairment and subsequently damage to the eye. In addition to the cornea and limbus, SCC is also relatively frequently located on the upper and lower eyelids or on the third eyelid (nictitating membrane). Ocular tumors are often locally invasive and have a high rate of recurrence.

In addition to genetic predisposition, environmental factors may contribute to the development of the tumor, including UV radiation, which directly affects the tumor suppressor gene p53, an important regulator of tumor suppression. Changes in the expression of this gene can lead to uncontrolled cell proliferation. Other factors include viruses, particularly equine papillomavirus type 2 (EcPV2), pigment type, and hormonal changes. Castrated horses are more susceptible to SCC.

Some horse breeds have a particularly high incidence of SCC in the limbal region, suggesting a possible genetic predisposition to the development of the disease.

The breeds with the highest incidence of SCC include Appaloosa and American Paint Horse. The white areas of their spotted coats are often insufficiently protected due to a lack of photoprotective pigment, which normally helps protect against the accumulation of UV-induced mutations. The conjunctiva and eye region are similarly affected. Several studies have identified chestnut coloration (e/e genotype, with no eumelanin production and increased photosensitivity) and gray depigmenting coloration, characterized by progressive loss of pigment, as risk factors.

Another breed with a relatively high number of diagnosed SCC cases is the Haflinger. The young age at diagnosis and high prevalence of the disease suggest a possible genetic predisposition. The high incidence may be associated with the chestnut coloration typical of the breed.

SCC is associated with a mutation in the DDB2 gene (g.11726667C>T). The main function of this gene is the repair of DNA damage caused by exposure to UV radiation.

In addition to the aforementioned Appaloosa, American Paint Horse, and Haflinger, SCC has also been reported in Belgian Draft Horse, Connemara Pony, Noriker, Percheron, Rocky Mountain Horse, and Welsh Pony.

Ocular squamous cell carcinoma is inherited in an autosomal recessive manner. The disease therefore develops in individuals that inherit the mutated allele from both parents. These individuals are designated P/P (positive/positive). Carriers of the mutated allele, designated N/P (negative/positive), have inherited the mutated allele from only one parent and do not show clinical signs. However, they can pass the mutation on to their offspring.

When two heterozygous carriers (N/P) are mated, theoretically 25% of the offspring will be clear, 50% will be carriers, and 25% will inherit the mutated allele from both parents and be affected by SCC. Mating a clear individual (N/N) with a carrier (N/P) theoretically results in 50% carriers and 50% clear offspring. If a carrier (N/P) is mated with an affected individual (P/P), theoretically 50% of the offspring will be affected and 50% will be carriers.

Regular eye examinations are recommended for horses diagnosed as P/P.

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Reference:
Bellone, Rebecca R., et al. “A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses.” International Journal of Cancer 141.2 (2017): 342–353.