Analysis of microphthalmia transcription factor expression in normal tissues and tumors, and comparison of its expression with S-100 protein, gp100, and tyrosinase in desmoplastic malignant melanoma

Microphthalmia transcription factor (Mitf) is a nuclear protein involved in the development of melanocytes and the regulation of melanin synthesis. Re cent studies have suggested that Mitf may be a more sensitive and specific melanocyte marker than S-100 protein and gp100. However, there is insuffici ent knowledge on the specificity of Mitf, and a systematic examination of i ts use for the recognition of desmoplastic melanoma has not yet been perfor med. In this study, we compared the expression of Mitf with S-100 protein, gp100, and tyrosinase in 20 desmoplastic melanomas by using the antibodies D5 (anti-Mitf). anti-S100P, HMB-45 (anti-gp100), and T311 (anti-tyrosinase) . All 20 melanomas were positive for S-100 protein, 7 were positive for Mit f, 6 for gp100, and 11 for tyrosinase. To examine the specificity of Mitf, a panel of normal tissue and 386 samples of miscellaneous tumors. including dermal and subcutaneous spindle cell lesions relevant for the differential diagnosis of desmoplastic melanoma, were examined by immuno-histochemistry . Furthermore, normal tissue samples were tested for Mitf mRNA by reverse t ranscriptase polymerase chain reaction (rt-PCR). Immunoreactivity For Mitf was seen not only in melanocytes of normal skin, but also in macrophages, l ymphocytes, fibroblasts, Schwann cells, and smooth muscle cells at various sites, and tumors derived thereof. Our results indicate that the antibody D 5 lacks sufficient sensitivity and specificity for widespread diagnostic us e. Especially in re-excisions, when immunohistochemistry is often needed to distinguish an inflamed scar tissue from tumor, the presence of immunoposi tive inflammatory cells and fibroblasts limits the diagnostic use of D5.