The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma
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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.
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).
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.
KeywordsHLA Ancestral haplotype 62.1 Malignant melanoma Survival Cox analysis
Human leucocyte antigen
Major histocompatibility complex
Ancestral HLA haplotype
Polymerase chain reaction
Healthy Swedish donors
Time from primary diagnosis to first metastasis
Survival time from metastasis
This study was mainly supported by grants from the Cancer Society in Stockholm and the King Gustaf V Jubilee Fund and the Swedish Cancer Society, the Karolinska Institute/Stockholm County ALF grant and the Deutsche Forschungsgemeinschaft (DFG) Se-585-10 (BS). We are also grateful for the financial support provided by the motility grant #040226# from “NordForsk, Holbergs gate 1, NO-0166 Oslo, NORWAY” to the NCEV network project. We thank Dr. Raja Choudhury for the reviewing of the manuscript.
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