Cancer Immunology, Immunotherapy

, Volume 58, Issue 10, pp 1599–1608

The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma

  • 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
Original Article

DOI: 10.1007/s00262-009-0669-8

Cite this article as:
Helgadottir, H., Andersson, E., Villabona, L. et al. Cancer Immunol Immunother (2009) 58: 1599. doi:10.1007/s00262-009-0669-8

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.

Keywords

HLAAncestral haplotype 62.1Malignant melanomaSurvivalCox analysis

Abbreviations

HLA

Human leucocyte antigen

MHC

Major histocompatibility complex

AHH

Ancestral HLA haplotype

PCR

Polymerase chain reaction

HSD

Healthy Swedish donors

MM

Malignant melanoma

OS

Overall survival

TTM1

Time from primary diagnosis to first metastasis

SFM1

Survival time from metastasis

Supplementary material

262_2009_669_MOESM1_ESM.pdf (22 kb)
Supplementary material 1 (PDF 22 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hildur Helgadottir
    • 1
  • Emilia Andersson
    • 1
  • Lisa Villabona
    • 1
  • Lena Kanter
    • 1
  • Henk van der Zanden
    • 2
    • 3
  • Geert W. Haasnoot
    • 3
  • Barbara Seliger
    • 4
  • Kjell Bergfeldt
    • 1
  • Johan Hansson
    • 1
  • Boel Ragnarsson-Olding
    • 1
  • Rolf Kiessling
    • 1
  • Giuseppe Valentino Masucci
    • 1
  1. 1.Department of Oncology-PathologyKarolinska Institute, Radiumhemmet, Karolinska University HospitalStockholmSweden
  2. 2.Europdonor FoundationLeidenThe Netherlands
  3. 3.Department of Immunohematology and Blood TransfusionLeiden University Medical CentreLeidenThe Netherlands
  4. 4.Institute of Medical ImmunologyMartin Luther University Halle-WittenbergHalle/SaaleGermany