title: Heterogeneity of Metastatic Melanoma:  Correlation of MITF With Its Transcriptional Targets MLSN1, PEDF, HMB-45, and MART-1.
abstract: OBJECTIVE
  Histologic and molecular heterogeneity is well recognized in malignant melanoma; however, the diversity of expression of new and classic melanoma markers has not been correlated in serial sections of metastases.
  
  
  METHODS
  We examined and correlated the expression of microphthalmia transcription factor (MITF) with its transcriptional targets, including melastatin (MLSN1/TRPM1), pigment epithelium-derived factor (SERPINF1/PEDF), SILV/PMEL17/GP100 (human melanoma black 45 [HMB-45]), and melanoma antigen recognized by T cells 1 (MART-1)/MLANA, in 13 melanoma metastases in lymph nodes of 13 patients. The expression levels and patterns of marker expression were recorded by a semiquantitative, 4-point ordinal reactivity method.
  
  
  RESULTS
  Our results showed a consistently robust and diffuse expression of MITF protein in 12 (92%) of 13 metastatic tumors compared with variable expression of MLSN1 (46%) messenger RNA or PEDF (75%), HMB-45 (54%), and MART-1 (46%) proteins.
  
  
  CONCLUSIONS
  Overall, in melanoma lymph node metastases, MITF protein expression was not tightly correlated with its gene targets. Moreover, the immunoreactivity for MITF, compared with MART-1 and HMB-45, was retained, supporting immunohistochemical detection of MITF as a more sensitive method of detecting metastatic melanoma.
authors: From the Cosmetic & Laser Surgery Institute, Kentfield, CA.
authors: Sarvenaz
authors: S
authors: Zand
authors: Department of Dermatology, Brigham and Women's Hospital, Boston, MA.
authors: Elizabeth
authors: E
authors: Buzney
authors: Dermatopathology Unit and Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Lyn M
authors: LM
authors: Duncan
authors: Departments of Dermatology and Pathology, University of Connecticut, Farmington. dadras@uchc.edu.
authors: Soheil S
authors: SS
authors: Dadras
mesh_terms: D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D058965:MART-1 Antigen / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D058950:Melanoma-Specific Antigens / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D050053:TRPM Cation Channels / Q000378:metabolism*; D058951:gp100 Melanoma Antigen; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D058965:MART-1 Antigen; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; D009414:Nerve Growth Factors; D015843:Serpins; D050053:TRPM Cation Channels; D058951:gp100 Melanoma Antigen; D000099174:Pigment Epithelium-Derived Factor; C548637:PMEL protein, human; C492059:TRPM1 protein, human
keywords: HMB-45; Lymph node; MART-1; MITF; Melanoma metastasis; Melastatin (MLSN1/TRPM1); PEDF