Abstract
Available data have led to a controversy on the relationship between human leukocyte antigen (HLA) and cutaneous malignant melanoma susceptibility or prognosis. Moreover, the influence of HLA-C on melanoma has not yet been well established. Therefore, the aim of the current study was to analyze the possible influence of the HLA system on melanoma susceptibility and prognosis in the Spanish population. For this purpose, HLA-A and HLA-B serotyping and HLA-C, HLA-DRB1, and HLA-DQB1 genotyping by polymerase chain reactions using sequence-specific oligonucleotide (PCR-SSO) and sequence-specific primer (PCR-SSP) were performed in 174 melanoma patients and 227 ethnically matched controls. The number of controls was increased up to 356 for HLA-C typing. Patients were stratified according to the histological subtypes of melanoma, sentinel lymph node status, tumor thickness, and ulceration of primary lesion. No HLA-A, HLA-B, HLA-DRB1, or HLA-DQB1 relationship with melanoma was observed for susceptibility or disease prognosis. However, the analysis of HLA-C locus showed that individuals homozygous for HLA-CLys80 were significantly more frequent within the patient than the control group. Remarkably, individuals homozygous for group 2 HLA-C alleles (HLA-CLys80) seem to be associated with metastatic progression of melanoma. In contrast, we found a negative association between group 1 HLA-C alleles (HLA-CAsn80) and disease susceptibility or metastasis development. In conclusion, although an association with HLA-A, HLA-B, HLA-DRB1, or HLA-DQB1 was not demonstrated, the study of the HLA-C locus revealed that the analysis of the dimorphism at position 80 in the α1 helix may help to evaluate the risk and prognosis of melanoma in our population.
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Acknowledgements
The authors wish to thank J.M. Alemany, M.J. Sanchis, M. Lopez, and M.C. Garcia Calatayud for their excellent technical assistance. This work was financially supported by the Seneca projects PI-400811/FS/01 and AR 1-02632/FS/02, by the Fondo de Investigacion Sanitaria (FIS) Program of Redes Tematicas de Investigacion, project G0/3104, and by Caja Murcia Foundation. J.A. Campillo is a postdoctoral researcher supported by the Spanish Health Ministry FIS (CM0300073).
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The contributions by José A. Campillo and Jorge A. Martínez-Escribano are equal, and the order of authorship is arbitrary
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Campillo, J.A., Martínez-Escribano, J.A., Muro, M. et al. HLA class I and class II frequencies in patients with cutaneous malignant melanoma from southeastern Spain: the role of HLA-C in disease prognosis. Immunogenetics 57, 926–933 (2006). https://doi.org/10.1007/s00251-005-0065-2
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DOI: https://doi.org/10.1007/s00251-005-0065-2