title: Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas.
abstract: BACKGROUND
  Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors.
  
  
  METHODS
  Sixty-two stage II-III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers.
  
  
  RESULTS
  We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count.
  
  
  CONCLUSIONS
  Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations.
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ellen H
authors.initials: EH
authors.lastname: de Moll
authors.forename: Yichun
authors.initials: Y
authors.lastname: Fu
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Qian
authors.forename: Sara H
authors.initials: SH
authors.lastname: Perkins
authors.forename: Shira
authors.initials: S
authors.lastname: Wieder
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Romain
authors.initials: R
authors.lastname: Remark
authors.forename: Sebastian G
authors.initials: SG
authors.lastname: Bernardo
authors.forename: Marina
authors.initials: M
authors.lastname: Moskalenko
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yao
authors.forename: Tammie
authors.initials: T
authors.lastname: Ferringer
authors.forename: Rui
authors.initials: R
authors.lastname: Chang
authors.forename: Jerry
authors.initials: J
authors.lastname: Chipuk
authors.forename: Basil A
authors.initials: BA
authors.lastname: Horst
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Birge
authors.forename: Robert G
authors.initials: RG
authors.lastname: Phelps
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Saenger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor