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(American Journal of Pathology. 1999;155:731-738.)
© 1999 American Society for Investigative Pathology

Regular Articles

Microphthalmia Transcription Factor

A Sensitive and Specific Melanocyte Marker for MelanomaDiagnosis

Roy King*, Katherine N. Weilbaecher{dagger}, Gaël McGill{dagger}, Edward Cooley*, Martin Mihm*{ddagger} and David E. Fisher{dagger}

From the Department of Dermatopathology,*
Albany Medical Center, Albany, New York; the Division of Pediatric Oncology,{dagger}
Dana Farber Cancer Institute and Children's Hospital, Boston, Massachusetts; and the Department of Dermatopathology,{ddagger}
Massachusetts General Hospital, Boston, Massachusetts

Malignant melanomas do not uniformly retain expression of melanocytic gene products—an observation associated with diagnostic dilemmas. Microphthalmia transcription factor (Mitf) is a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes. It serves as a master regulator in modulating extracellular signals, such as those triggered by {alpha}-MSH and c-Kit ligand. Because of its central role in melanocyte survival and to assess its potential use as a histopathological marker for melanoma, Mitf expression was examined in histologically confirmed human melanoma specimens. Western blot analysis of melanoma cell lines revealed consistent expression of two Mitf protein isoforms differing by MAP kinase-mediated phosphorylation. In a series of 76 consecutive human melanoma surgical specimens, 100% stained positively for Mitf with a nuclear pattern of reactivity. In a side-by-side comparison, Mitf staining was positive in melanomas that failed to stain for either HMB-45 or S-100, the most common currently used melanoma markers. Of 60 non-melanoma tumors, none displayed nuclear Mitf staining and two displayed cytoplasmic staining. Although Mitf does not distinguish benign from malignant melanocytic lesions, for invasive neoplasms it appears to be a highly sensitive and specific histopathological melanocyte marker for melanoma.




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