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The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma
Authors:Hildur Helgadottir  Emilia Andersson  Lisa Villabona  Lena Kanter  Henk van der Zanden  Geert W. Haasnoot  Barbara Seliger  Kjell Bergfeldt  Johan Hansson  Boel Ragnarsson-Olding  Rolf Kiessling  Giuseppe Valentino Masucci
Affiliation:(1) Department of Oncology-Pathology, Karolinska Institute, Radiumhemmet, Karolinska University Hospital, 171 76 Stockholm, Sweden;(2) Europdonor Foundation, Leiden, The Netherlands;(3) Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands;(4) Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
Abstract:Purpose  We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with stage III–IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the prognosis in stage III–IV malignant melanoma patients. Patients and methods  A cohort of metastatic malignant melanoma patients (n = 91), in stage III (n = 26) or IV (n = 65) were analysed for HLA-A, -B, -Cw and -DRB1 types by PCR/sequence-specific primer method. The frequencies of HLA alleles in the patients were compared to that of healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined by Kaplan–Meier and Cox analysis. Results  The presence of the AHH 62.1 in clinical stage IV patients was significantly and independently associated with the worst survival rate recorded from the appearance of metastasis (HR = 2.14; CI = 1.02–4.4; P = 0.04). In contrast, the period from the primary diagnosis to metastasis was the longest in patients with this haplotype (HR = 0.40; CI = 0.17–0.90; P = 0.02). Conclusions  Melanoma patients in our cohort with 62.1 AHH which is associated with autoimmune diseases have an initial strong anti-tumour control with longer metastasis-free period. These patients have rapid progression after the appearance of metastasis, responding poorly to chemo- or/and immunotherapy. This apparently paradoxical clinical process could be due to the interplay between tumour clones escape and immune surveillance ending up with a rapid disease progression. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Keywords:HLA  Ancestral haplotype 62.1  Malignant melanoma  Survival  Cox analysis
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