Uveal melanoma (UM) continues to be associated with a high mortality rate of up to 50% due to metastatic spread primarily to the liver. Currently there are relatively effective treatments for the primary tumor, though the management of the metastatic disease remains inadequate. Conventional diagnostic tools have a low sensitivity for detecting metastasis, and early detection of metastatic spread would allow more treatment options that could ultimately increase survival of UM patients. Advanced proteomic methods have already helped to find potential biomarkers associated with UM pathogenesis and metastasis. In the present review we discuss the field of proteomics in relation to studies elucidating biomarkers of UM, where proteins such as S-100β, osteopontin (OPN), and melanoma inhibitory activity (MIA) have been shown to be associated with metastasis. 1. Introduction Uveal melanoma (UM) is an ocular cancer involving the uveal tract (iris, ciliary body, and the choroid). The incidence is approximately 4.3 per million/year in the United States occurring mostly amongst white males [1]. With treatment UM has a 5-year-survival rate of 77–84% [2–4]. Prognosis depends on a number of factors including primary tumor size, time of diagnosis, and whether metastasis is present [5, 6]. Larger tumors have a mortality rate of approximately 50% shortly after diagnosis, and medium sized tumors also have a similar mortality rate when measured 15 years after primary tumor treatment [4, 7, 8]. Metastatic disease usually involves the liver and almost always leads to death within 15 months [6]. It is believed that that most choroidal, perhaps most uveal, melanomas origin from transformed benign naevus [9]. Clinically the primary diagnosis of UM of the choroid often involves decreased visual acuity and scotoma secondary to retinal detachment, with slit lamp biomicroscopy showing melanotic or amelanotic tumor with or without orange dusting. The diagnosis is often supported by an ultrasound investigation showing acoustic hollowness [9–11]. Primary tumor is treated with either brachytherapy using radioactive plaques in an effort to preserve the tissues of the eye or enucleation. There is no difference in survival rate, between these two treatments, for medium and large sized tumors [7]. Metastasis is searched for but seldom found at the primary diagnosis, which often develops in the following months to years [12]. So far the best methods for detecting metastasis are nonspecific liver enzymes serum concentration (lactate dehydrogenase (LD), alkaline phosphatase (AP), aspartate
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