title: Down-regulation of proteasomal subunit MB1 is an independent predictor of improved survival in ovarian cancer.
abstract: OBJECTIVE
  To investigate the expression and to determine the prognostic impact of components of the antigen processing and presentation pathway (APPP) in ovarian cancer.
  
  
  METHODS
  Expression of MB1, LMP7, TAP1, TAP2, ERp57, ERAP1, beta(2)-microglobulin and the alpha-chains, HLA-B/C and HLA-A, of the MHC class I molecules was evaluated on tissue microarrays containing primary tumor samples from 232 FIGO stages I-IV ovarian cancer patients. Expression levels were correlated to clinicopathological data and disease specific (DSS) survival.
  
  
  RESULTS
  Patients with expression of all components of the MHC class I complex, i.e. HLA-A(+)-beta(2)-m(+) and HLA-B/C(+)-beta(2)-m(+) patients, more often had expression of LMP7, a component of the immunoproteasome than patients with other phenotypes (p<0.001). These patients were also more prone to loss of MB1, part of the constitutive multicatalytic proteasome (p<0.05). Nuclear MB1 expression was an independent predictor of worse DSS (HR 1.94, 95% CI 1.16-3.26, p=0.012). The HLA-B/C(+)-beta(2)-m(+) phenotype was an independent predictor of a better prognosis (HR 0.63, 95% CI 0.40-0.99, p=0.047). Median DSS was longer for patients with normal nuclear expression of LMP7 (57.4 vs. 31.0 months, p=0.029).
  
  
  CONCLUSIONS
  The prognostic influence of the proteasomal subunit MB1 and the MHC class I complex in ovarian cancer provides a rationale for targeting these specific APPP components in ovarian cancer.
authors.affiliation: Department of Gynecological Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ninke
authors.initials: N
authors.lastname: Leffers
authors.forename: Marloes J M
authors.initials: MJ
authors.lastname: Gooden
authors.forename: Anna A
authors.initials: AA
authors.lastname: Mokhova
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.forename: Klaske A
authors.initials: KA
authors.lastname: Ten Hoor
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Toos
authors.initials: T
authors.lastname: Daemen
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000276:immunology; D000626:Aminopeptidases / Q000096:biosynthesis / Q000276:immunology; D017951:Antigen Presentation; D051925:CD79 Antigens / Q000096:biosynthesis* / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000276:immunology; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000276:immunology; D015236:HLA-C Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000276:immunology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000276:immunology; D019704:Protein Disulfide-Isomerases / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D051925:CD79 Antigens; C497881:CD79A protein, human; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015778:Minor Histocompatibility Antigens; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human