Immunogenetics

, Volume 65, Issue 5, pp 333–343

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

  • 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 Álvarez-López
  • Jorge A. Martínez-Escribano
Original Paper

DOI: 10.1007/s00251-013-0682-0

Cite this article as:
Campillo, J.A., Legaz, I., López-Álvarez, M.R. et al. Immunogenetics (2013) 65: 333. doi:10.1007/s00251-013-0682-0

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.

Keywords

MelanomaKIR receptorsHLA class I ligandsSentinel lymph node metastasisUlceration

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • José A. Campillo
    • 1
  • Isabel Legaz
    • 1
  • M. Rocío López-Álvarez
    • 1
  • José Miguel Bolarín
    • 1
  • Beatriz Las Heras
    • 1
  • Manuel Muro
    • 1
  • Alfredo Minguela
    • 1
  • María R. Moya-Quiles
    • 1
  • Rosa Blanco-García
    • 1
  • Helios Martínez-Banaclocha
    • 1
  • Ana M. García-Alonso
    • 1
  • M. Rocío Álvarez-López
    • 1
  • Jorge A. Martínez-Escribano
    • 2
  1. 1.Immunology DepartmentVirgen de la Arrixaca University HospitalMurciaSpain
  2. 2.Dermatology DepartmentVirgen de la Arrixaca University HospitalMurciaSpain