title: The Influence of HLA and KIR Genes on Malignant Melanoma Development and Progression.
abstract: Many studies have described the role of killer immunoglobulin-like receptors (KIRs) and their cognate human leukocyte antigen (HLA) class I ligands in the immune protection against melanoma, but the effect of these markers on intra-individual variations in tumor development and progression has remained less clear. We performed KIR, HLA, and KIR/ligand analysis in 283 patients with malignant melanoma in order to evaluate their integrated influence on disease stage and progression. The patients were grouped according to AJCC staging, histological type of the primary tumor, progression, and survival rate. Analysis of HLA class I alleles revealed positive association of HLA-C*14 (Pc = 0.026, OR = 5.99) and negative association of HLA-C*02 (Pc = 0.026, OR = 0.43) with the disease. Decreased frequency of KIR2DS5 was observed in patients with rapid progression, as compared to those with slow progression. KIR BB genotype was prevalent in patients with metastasis (p = 0.004, OR = 0.025). KIR AA genotype was nearly twice as frequent in rapidly progressive cases, but without statistical relevance (p = 0.055, OR = 2.6). Significantly increased frequency of KIR2DL2 in the presence of C1 ligand (strong inhibition) was found in patients with AJCC III and IV, as compared to individuals with AJCC I stage (p = 0.045, OR = 1.93). In summary, our data imply that KIR/ligand gene content in patients could modulate the disease course towards unfavorable tumor behavior.
authors.affiliation: Department of Clinical Immunology with Stem Cell Bank, Alexandrovska University Hospital, Medical University, 1431, Sofia, Bulgaria. sneji_jm@yahoo.com.
authors.forename: Snezhina Mihailova
authors.initials: SM
authors.lastname: Kandilarova
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Paschen
authors.affiliation: Department of Clinical Immunology with Stem Cell Bank, Alexandrovska University Hospital, Medical University, 1431, Sofia, Bulgaria.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Mihaylova
authors.affiliation: Department of Clinical Immunology with Stem Cell Bank, Alexandrovska University Hospital, Medical University, 1431, Sofia, Bulgaria.
authors.forename: Milena
authors.initials: M
authors.lastname: Ivanova
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Clinical Immunology with Stem Cell Bank, Alexandrovska University Hospital, Medical University, 1431, Sofia, Bulgaria.
authors.forename: Elissaveta
authors.initials: E
authors.lastname: Naumova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D020816:Amino Acid Motifs; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015791:HLA-A3 Antigen / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology; D008024:Ligands; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D054344:Receptors, KIR2DL3 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D000096142:Cutaneous Malignant Melanoma
chemical_list: D006680:HLA Antigens; D015791:HLA-A3 Antigen; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3
keywords: Human leukocyte antigens (HLA); Inhibitory killer immunoglobulin-like receptors (KIR); Malignant melanoma; Progression