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.