Abstract 5317: HLA-E and HLA-G tumor expression is of prognostic value for clinical outcome of early breast cancer patients, but exclusively in classical HLA class I tumor-negative patients

Abstract

Abstract Background Non-classical human leukocyte antigens (HLA), HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and related the results to tumor expression of classical HLA class I molecules, as together these cell surface molecules may determine natural killer (NK) cell responses. Material and Methods Our study population (n=677) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1995. Tissue micro array (TMA) sections of formalin-fixed paraffin-embedded tumors were immunohistochemically stained for HLA-E and HLA-G. For evaluation of HLA-E and HLA-G expression and the combined variable, HLA-EG, a binary score was used. Expression of classical HLA class I expression was previously determined. Results HLA-E, HLA-G and HLA-EG were expressed in breast tumors in 50%, 60% and 23% of patients respectively. Remarkably, only in patients with loss of classical HLA class I tumor expression, expression of HLA-E (p=0.027), HLA-G (p=0.035) and HLA-EG (p=0.001) resulted in a worse relapse free period. An interaction was found between classical and non-classical HLA class I expression (p=0.002), suggestive for a biological connection. Conclusions We have demonstrated that expression of HLA-E and HLA-G are important factors in the prediction of clinical outcome of breast cancer patients, but exclusively in patients with classical HLA class I negative tumors. HLA-E and HLA-G expression may specifically prevent NK-cell recognition by the host in this subset of tumors. These results provide further evidence that breast cancer is highly immunogenic, but also capable of evading tumor eradication by the host immune system in which both T cells and NK cells play a role. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5317.