Microphthalmia transcription factor - A sensitive and specific marker for malignant melanoma in cytologic specimens

BACKGROUND. The diagnosis of melanoma can be difficult because of shared cy tomorphology with other malignant neoplasms. The most commonly used melanoc ytic markers, anti-S-100 protein and HMB-45 antigen, have limited specifici ty and sensitivity, respectively. Microphthalmia transcription factor (Mitf ) is a nuclear transcription factor critical for the development and surviv al of melanocytes and has been shown as a sensitive and specific marker for melanoma in histologic specimens. METHODS. To evaluate the efficacy of Mitf as a marker for melanoma in cytol ogic preparations, 81 cell blocks from 44 patients with melanoma and 37 pat ients with nonmelanoma malignancies (29 patients with carcinoma, 4 patients with mesotheliomas, 2 patients with lymphoma, and 2 patients with islet ce ll tumors) were stained with monoclonal antibodies against Mitf (clone D5), S-100 protein, and HMB-45 antigen. The staining was evaluated blindly by t hree independent observers. The presence of nuclear staining for Mitf and c ytoplasmic staining for S-100 protein or HMB-45 antigen in > 10% of tumor c ells was considered positive staining for each antigen. RESULTS. Forty-four melanomas (100%), including all 3 spindle-cell melanoma s, were positive for Mitf. All nonmelanoma neoplasms were negative with onl y one exception: One mammary carcinoma showed rare (< 10%), weak nuclear st aining with Mitf. The sensitivity and specificity of Mitf as a marker for m elanoma were both 100%, whereas the sensitivity of HMB-45 antigen was 90.4% , and the specificity of S-100 protein was 70.3%. CONCLUSIONS. Mitf is a sensitive and specific marker for malignant melanoma , including the spindle-cell variant, in cytologic specimens and may be sup erior to the current standard melanocytic markers, S-100 protein and HMB-45 antigen. (C) 2001 American Cancer Society.