title: Marker Protein Expression Combined With Expression Heterogeneity is a Powerful Indicator of Malignancy in Acral Lentiginous Melanomas.
abstract: METHODS
  Samples of acral lentiginous melanomas (ALMs) were obtained from the Department of Pathology at Escola Paulista de Medicina-Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Demographic, clinical, and follow-up data were obtained from the charts of Hospital São Paulo. From 2 tissue microarrays containing 60 nevi and quadruplicate samples of ≥1.0-mm of 49 ALM, sections were stained to evaluate SCF, KIT, BRAF, CYCLIND1, MYC, and PTEN immunohistochemical protein expression.
  
  
  RESULTS
  Nevi and ALM from 2006 to 2010 were reviewed and collected. All specimens were in the vertical growth phase, and histopathological parameters indicated that tumors were at an advanced stage at diagnosis. Average tumor thickness was 6.95 mm, 63% were ulcerated, average mitotic index was 5 mitotic cells per mm, and 43% were at Clark's level V. Compared with nevi, the χ test showed that ALM significantly correlated with SCF protein expression (P = 0.001) and expression heterogeneity (P < 0.000). Similar findings were observed for KIT (P = 0.005, P = 0.003, respectively), MYC (P < 0.000, P < 0.000), and PTEN (P = 0.005, P < 0.000). Malignancy did not correlate with BRAF and CYCLIN D1 expression (P = 0.053 and P = 0.259, respectively), but it did significantly correlate with their heterogeneous expression (P < 0.000, P = 0.024, respectively). Combined protein expression had an odds ratio of greater malignancy when BRAF and MYC were positive and/or heterogeneously expressed (OR of 78 and 95, respectively).
  
  
  CONCLUSIONS
  We show that marker protein expression, when combined with heterogeneous expression as shown by immunohistochemistry, is a powerful indicator of malignancy in ALMs, especially, when protein pairs are combined.
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cintra Lopes Carapeto
authors.forename: Andréia
authors.initials: A
authors.lastname: Neves Comodo
authors.forename: Andressa
authors.initials: A
authors.lastname: Germano
authors.forename: Daiane
authors.initials: D
authors.lastname: Pereira Guimarães
authors.forename: Denise
authors.initials: D
authors.lastname: Barcelos
authors.forename: Mariana
authors.initials: M
authors.lastname: Fernandes
authors.forename: Gilles
authors.initials: G
authors.lastname: Landman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D012878:Skin Neoplasms; D046888:Tissue Array Analysis; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor