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

• Abstract: 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.
• Authors: Akash M Mehta, Ekaterina S Jordanova, Gemma G Kenter, Soldano Ferrone, Gert-Jan Fleuren (Affiliation: Department of Pathology, Leiden University Medical Centre, P1-40, L1-Q, 2333 ZA Leiden, The Netherlands.)
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 57 Issue 2 Pg. 197-206 (Feb 2008) ISSN: 0340-7004 [Print] Germany
• PMID: 17622526 (Publication Type: Journal Article)

Chemical References

• ARTS-1 protein, human
• ATP-Binding Cassette Transporters
• Histocompatibility Antigens Class I
• TAP1 protein, human
• Aminopeptidases

Topics

• 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-Meiers Estimate
• Middle Aged
• Prognosis
• Tissue Array Analysis
• Uterine Cervical Neoplasms (immunology, mortality, pathology)