KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis.
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.
Immunology Department, Virgen de la Arrixaca University Hospital, El Palmar, Murcia, Spain. jcampillo68@hotmail.com
José A
JA
Campillo
Isabel
I
Legaz
M Rocío
MR
López-Álvarez
José Miguel
JM
Bolarín
Beatriz
B
Las Heras
Manuel
M
Muro
Alfredo
A
Minguela
María R
MR
Moya-Quiles
Rosa
R
Blanco-García
Helios
H
Martínez-Banaclocha
Ana M
AM
García-Alonso
M Rocío
MR
Alvarez-López
Jorge A
JA
Martínez-Escribano
D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D054344:Receptors, KIR2DL3 / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000556:secondary
D014408:Biomarkers, Tumor; D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D054344:Receptors, KIR2DL3