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.
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 cancerpatients. 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: Marloes Gooden; Margit Lampen; Ekaterina S Jordanova; Ninke Leffers; J Baptist Trimbos; Sjoerd H van der Burg; Hans Nijman; Thorbald van Hall Journal: Proc Natl Acad Sci U S A Date: 2011-06-13 Impact factor: 11.205
Authors: Renee Vermeij; Toos Daemen; Geertruida H de Bock; Pauline de Graeff; Ninke Leffers; Annechien Lambeck; Klaske A ten Hoor; Harry Hollema; Ate G J van der Zee; Hans W Nijman Journal: Clin Dev Immunol Date: 2010-09-15
Authors: N Leffers; R S N Fehrmann; M J M Gooden; U R J Schulze; K A Ten Hoor; H Hollema; H M Boezen; T Daemen; S de Jong; H W Nijman; A G J van der Zee Journal: Br J Cancer Date: 2010-07-27 Impact factor: 7.640
Authors: Wanqi Wang; Noor A Lokman; Tannith M Noye; Anne M Macpherson; Martin K Oehler; Carmela Ricciardelli Journal: Cancer Drug Resist Date: 2021-06-19