Role for microphthalmia transcription factor in the diagnosis of metastatic malignant melanoma

Microphthalmia transcription factor (Mitf), a protein critical for the embryonic development and postnatal viability of melanocytes, is a master lineage regulator and modulates extracellular signals. Recently, an anti-Mitf antibody, D5, was shown to be both a sensitive and a specific marker of epithelioid melanoma. Those data suggested that Mitf expression was specific for melanocytic differentiation because it was not detected in six different carcinoma types. To broaden the spectrum of melanomatous and nonmelanomatous tumors tested with this antibody, the authors investigated the sensitivity and specificity of the D5 anti-Mitf antibody in 36 metastatic melanomas and 102 nonmelanomatous tumors. Twenty-nine of 36 (81%) melanomas examined were reactive for D5. Of these, 29 of 32 (91%) epithelioid melanomas were reactive, whereas all 4 melanomas with spindle cell morphology were nonreactive. Six of 102 (5.8%) nonmelanomatous tumors (1 breast carcinoma, 1 malignant mixed mullerian tumor, 2 renal cell carcinomas, and 2 leiomyosarcomas) were reactive for D5. All melanomas were reactive for S-100 protein (a criteria for inclusion in the study), whereas 8 of 102 (7.8%) of nonmelanomatous tumors were reactive. Twenty-five of 36 melanomas (69%) were reactive for HMB-45, whereas no nonmelanomatous tumors were reactive. Twenty-one of 28 (75%) melanomas were reactive for Melan-A. Reactivity for Melan-A was detected in 5 of 102 (4.9%) nonmelanomatous tumors. As with D5, HMB-45 and Melan-A failed to detect all spindle-cell melanomas. Results of this study confirm that D5 is a sensitive marker for epithelioid melanomas; however, the authors found D5 neither quite as sensitive nor quite as specific as in previous studies. Nevertheless, the authors believe that positive staining for D5 when taken in clinical, histologic, and immunohistochemical context may be diagnostically useful. In particular, D5 is helpful in the evaluation of epithelioid neoplasms, but not spindle-cell tumors.