title: Microphthalmia transcription factor: a sensitive and specific marker for malignant melanoma in cytologic specimens.
abstract: BACKGROUND
  The diagnosis of melanoma can be difficult because of shared cytomorphology with other malignant neoplasms. The most commonly used melanocytic markers, anti-S-100 protein and HMB-45 antigen, have limited specificity and sensitivity, respectively. Microphthalmia transcription factor (Mitf) is a nuclear transcription factor critical for the development and survival 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 cytologic preparations, 81 cell blocks from 44 patients with melanoma and 37 patients with nonmelanoma malignancies (29 patients with carcinoma, 4 patients with mesotheliomas, 2 patients with lymphoma, and 2 patients with islet cell tumors) were stained with monoclonal antibodies against Mitf (clone D5), S-100 protein, and HMB-45 antigen. The staining was evaluated blindly by three independent observers. The presence of nuclear staining for Mitf and cytoplasmic staining for S-100 protein or HMB-45 antigen in > 10% of tumor cells was considered positive staining for each antigen.
  
  
  RESULTS
  Forty-four melanomas (100%), including all 3 spindle-cell melanomas, were positive for Mitf. All nonmelanoma neoplasms were negative with only one exception: One mammary carcinoma showed rare (< 10%), weak nuclear staining with Mitf. The sensitivity and specificity of Mitf as a marker for melanoma 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 superior to the current standard melanocytic markers, S-100 protein and HMB-45 antigen.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 35249-6823, USA. cdorvault@earthlink.net
authors.forename: C C
authors.initials: CC
authors.lastname: Dorvault
authors.forename: K N
authors.initials: KN
authors.lastname: Weilbaecher
authors.forename: H
authors.initials: H
authors.lastname: Yee
authors.forename: D E
authors.initials: DE
authors.lastname: Fisher
authors.forename: L A
authors.initials: LA
authors.lastname: Chiriboga
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: D C
authors.initials: DC
authors.lastname: Chhieng
mesh_terms: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D008545:Melanoma / Q000473:pathology* / Q000556:secondary; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins / Q000032:analysis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D009418:S100 Proteins / Q000032:analysis; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497234:MITF protein, human; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; D009418:S100 Proteins; D014157:Transcription Factors