title: The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Radiumhemmet, Karolinska University Hospital, 171 76, Stockholm, Sweden.
authors.forename: Hildur
authors.initials: H
authors.lastname: Helgadottir
authors.forename: Emilia
authors.initials: E
authors.lastname: Andersson
authors.forename: Lisa
authors.initials: L
authors.lastname: Villabona
authors.forename: Lena
authors.initials: L
authors.lastname: Kanter
authors.forename: Henk
authors.initials: H
authors.lastname: van der Zanden
authors.forename: Geert W
authors.initials: GW
authors.lastname: Haasnoot
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.forename: Kjell
authors.initials: K
authors.lastname: Bergfeldt
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Boel
authors.initials: B
authors.lastname: Ragnarsson-Olding
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
authors.forename: Giuseppe Valentino
authors.initials: GV
authors.lastname: Masucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; C047431:HLA-Cw1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains