title: Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.
abstract: BACKGROUND
  The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized.
  
  
  OBJECTIVE
  To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance.
  
  
  METHODS
  S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted.
  
  
  RESULTS
  Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival.
  
  
  CONCLUSIONS
  Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Hollis
authors.initials: H
authors.lastname: Viray
authors.forename: William R
authors.initials: WR
authors.lastname: Bradley
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Schalper
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Bonnie E
authors.initials: BE
authors.lastname: Gould Rothberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D058965:MART-1 Antigen / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D058950:Melanoma-Specific Antigens / Q000378:metabolism*; D008875:Middle Aged; D009418:S100 Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D058951:gp100 Melanoma Antigen
chemical_list: D014408:Biomarkers, Tumor; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008543:Melanins; D058950:Melanoma-Specific Antigens; C548637:PMEL protein, human; D009418:S100 Proteins; D058951:gp100 Melanoma Antigen
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