title: Association of antigen-processing machinery and HLA antigen phenotype of melanoma cells with survival in American Joint Committee on Cancer stage III and IV melanoma patients.
abstract: Because changes in the expression level of antigen-processing machinery (APM) components and HLA class I and II antigens in melanoma cells are expected to affect their interactions with the immune system of the host, we assessed the clinical relevance of quantitative variations in the expression of these molecules in melanoma lesions. Short-term (<10 in vitro passages) melanoma cell lines isolated from 85 American Joint Committee on Cancer (AJCC) stage III and IV patients were stained with APM component and HLA class I antigen-specific and HLA class II antigen-specific monoclonal antibodies and analyzed by flow cytometry. The phenotype of all tumors was characterized by intertumor and intratumor heterogeneity in the expression of all the markers and by significant correlations in the level of expression of markers belonging to the HLA class I antigen-processing and presentation pathway. Hierarchical clustering of the mean fluorescence intensity data defined two main clusters of tumors. The corresponding groups of patients differed significantly in the overall survival but not in other relevant clinical variables, including AJCC stage and therapy received after surgery. Cox regression analysis showed that beta2-microglobulin and HLA class II antigen expression were significantly associated with patients' survival. This evidence was corroborated by the immunohistochemical analysis for HLA class II antigen expression of melanoma lesions from an unrelated group of 52 AJCC stage III and IV patients. These results suggest that quantitative variations in APM component and HLA expression in melanoma lesions from AJCC stage III and IV patients may have an effect on the clinical course of the disease.
authors.affiliation: Unit of Human Tumors Immunobiology and Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. andrea.anichini@istitutotumori.mi.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Anichini
authors.forename: Roberta
authors.initials: R
authors.lastname: Mortarini
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nonaka
authors.forename: Alessandra
authors.initials: A
authors.lastname: Molla
authors.forename: Claudia
authors.initials: C
authors.lastname: Vegetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Montaldi
authors.forename: Xinhui
authors.initials: X
authors.lastname: Wang
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D045744:Cell Line, Tumor; D006680:HLA Antigens / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009367:Neoplasm Staging
chemical_list: D006680:HLA Antigens