title: High frequency of melanoma-associated antigen or HLA class I loss does not correlate with survival in primary melanoma.
abstract: Melanoma-associated antigens are at the center of many immunotherapeutic trials in melanoma. Little is known about the impact of antigen expression on the natural course of disease. We stained 110 cases of primary melanoma with a median follow-up of 13 years (range 10-18 years) for melanoma-associated antigens gp100, MelanA/MART-1, MAGE-3, tyrosinase, and for HLA class I molecules. Of 91 cases evaluated, we found immunoreactivity for gp100, MelanA/MART-1, and tyrosinase in 88%, 80%, and 87% of primary tumors, respectively, for MAGE-3 in 37% and for HLA class I in 86% of primary tumors. Loss, that is, heterogeneous expression within primary tumors, was most pronounced for gp100 (73% of primary tumors) and least for MAGE-3 (27% of primary tumors). MelanA/MART-1 and tyrosinase expression loss was 58% and 59% of primary tumors, respectively. There was a high rate of expression loss for HLA class I (74%). Univariate and multivariate statistical analysis of expression in primary tumors and loss of melanoma antigens as well as HLA class I in individual primary tumors showed no significant correlation to overall survival. Loss of gp100 and loss of tyrosinase expression showed a negative survival trend over homogeneous expression of these antigens, although not reaching statistical significance (P = 0.08 and P = 0.09, respectively). We conclude that loss of melanoma antigen expression as well as HLA class I expression is a frequent observation in primary melanoma. However, no statistically significant correlation between loss of these antigens in individual primary tumors and negative impact on overall survival was found in our cohort.
authors.affiliation: Department of Dermatology, University Hospital Zürich, Switzerland. gfl@hofbauer.ch
authors.forename: Günther F L
authors.initials: GF
authors.lastname: Hofbauer
authors.forename: Andrea
authors.initials: A
authors.lastname: Burkhart
authors.forename: Georges
authors.initials: G
authors.lastname: Schüler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Günter
authors.initials: G
authors.lastname: Burg
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D015996:Survival Rate; D013997:Time Factors; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase