Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

Cancer Immunol Immunother. 2008 Feb;57(2):197-206. doi: 10.1007/s00262-007-0362-8. Epub 2007 Jul 12.


HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, beta(2)-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P<0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P=0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P<0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P<0.05 and HR 2.84; P<0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopeptidases / metabolism
  • Antigen Presentation / immunology*
  • Disease-Free Survival
  • Down-Regulation
  • Female
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Prognosis
  • Tissue Array Analysis
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology*


  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Histocompatibility Antigens Class I
  • Minor Histocompatibility Antigens
  • TAP1 protein, human
  • Aminopeptidases
  • ERAP1 protein, human