KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis.

Abstract

Natural killer and CD8(+) T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P < 0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (Pc = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (Pc = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(-)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(-)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis.

• Authors: José A Campillo, Isabel Legaz, M Rocío López-Álvarez, José Miguel Bolarín, Beatriz Las Heras, Manuel Muro, Alfredo Minguela, María R Moya-Quiles, Rosa Blanco-García, Helios Martínez-Banaclocha, Ana M García-Alonso, M Rocío Alvarez-López, Jorge A Martínez-Escribano
• Journal: Immunogenetics (Immunogenetics) Vol. 65 Issue 5 Pg. 333-43 (May 2013) ISSN: 1432-1211 [Electronic] United States
• PMID: 23370861 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• HLA-C Antigens
• KIR2DL3 protein, human
• Receptors, KIR2DL3

Topics

• Biomarkers, Tumor (genetics)
• Female
• Genetic Predisposition to Disease
• Genetic Variation (genetics)
• Genotype
• HLA-C Antigens (genetics)
• Humans
• Lymphatic Metastasis
• Male
• Melanoma (genetics, pathology)
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Single-Stranded Conformational
• Prognosis
• Receptors, KIR2DL3 (genetics)
• Skin Neoplasms (genetics, secondary)