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, β 2 -microglobulin and the α-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 + –β 2 -m + and HLA-B/C + –β 2 -m + patients, more often had expression of LMP7, a component of the immunoproteasome than patients with other phenotypes ( p p p =0.012). The HLA-B/C + –β 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.