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 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.
Dorvault
C C
CC
Department of Pathology, University of Alabama at Birmingham, 35249-6823, USA. cdorvault@earthlink.net
Weilbaecher
K N
KN
Yee
H
H
Fisher
D E
DE
Chiriboga
L A
LA
Xu
Y
Y
Chhieng
D C
DC
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*
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