Constitutive and cytokine induced expression of melanocortin 1 receptor (mc1r) in uveal malignant melanoma
Uveal melanoma is a highly malignant tumor of the eye and it is the most common primary ocular cancer among adults. Uveal melanoma has a different expression pattern of surface markers compared to cutaneous melanoma. Recently, we have described a strong expression of melanocortin 1 receptor (MC1R), a melanoma specific marker, in primary and metastatic cutaneous melanomas. In the present study, we have analyzed the expression of MC1R in uveal melanomas and compared it with other common markers used for diagnosis. METHODS: Seventeen primary uveal melanomas were immunolabeled with a panel of antibodies that included S100, HMB-45, A103 and the novel monoclonal antibody MP1-1C11, which recognizes the extra cellular region of MC1R. RESULTS: The results were evaluated according to an arbitrary scale: -, +/-, +, on the basis of the intensity of the immune reactivity. The MC1R protein was detected in 95 percent (17/18) of the tested melanoma tissues, including a lever metastasis.
HMB-45 stained 66 percent (8/12) of tested melanomas. In addition, we found that the sensitivity for S100 was lower in uveal than in cutaneuos melanoma. S100 was detected only in 33 percent (5/15) of the analyzed samples. The antibody directed to MART-1 (A103) recognized 4 of 6 ocular melanoma tissues. We also demonstrated that surface expression of MC1R is up regulated in vitro by different cytokines such as, IFN-?, TNF, and IL-10 which may be relevant for antibody mediated immunotherapy. CONCLUSIONS: MC1R protein is more frequently expressed in uveal melanomas than the proteins recognized by HMB-45 and S100 antibodies and might therefore also be included as target for the antibody panel used for diagnosis of uveal melanocytic lesions.