Background: HMB-45, an antibody directed against a premelanosome glycoprotein, has thus far been considered the most specific antibody for the immunocytochemical substantiation of the diagnosis of malignant melanoma (MM). A recently described antigen, MART-1, is a transmembrane protein that is present in normal melanocytes and widely expressed in MM. Antibodies to MART-1 have recently become commercially available. Both HMB-45 and MART-1 form the basis of ongoing immunotherapy protocols at the National Institutes of Health/National Cancer Institute.
Methods: The authors evaluated 207 lesions from 160 patients with metastatic MM procured via fine-needle aspiration (FNA) for expression of MART-1 (clone M2-7C10) and HMB-45 prior to commencement of immunotherapy. FNAs were performed on subcutaneous soft tissue masses (190 lesions), lung (8 lesions), liver (5 lesions), pancreas (3 lesions), and brain (1 lesion). To test the specificity of the monoclonal antibody directed against MART-1, the authors evaluated its reactivity in normal tissues as well as in various nonpigmented neoplasms that are often included in the differential diagnosis of MM.
Results: Of all lesions tested, 13 (6%) were negative for both MART-1 and HMB-45. Of all patients tested, 20% had 1 or more lesions that were non-immunoreactive with HMB-45, whereas only 10% had 1 or more lesions that were nonimmunoreactive for MART-1. Eight percent of the lesions tested were negative for MART-1 only, whereas 16% of lesions tested were negative for HMB-45 only. In 35% of the lesions, MART-1 stained more cells than HMB-45. In 13%, MART-1 stained fewer cells than HMB-45, and in 52% both antibodies stained an equivalent number of cells. All samples of normal tissue were negative for staining with MART-1, as were the nonpigmented lesions tested. Melanocytes in normal skin samples stained positively for MART-1.
Conclusions: The MART-1 antibody is a superior immunohistochemical marker for the diagnosis of MM. It has the potential to become the preferred antibody over HMB-45 for the diagnosis of metastatic MM in FNA material, as MART-1 stains a higher percentage of lesions in a higher percentage of patients than does HMB-45.