Population Based Assessment of MHC Class I Antigens Down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from Benign Breast Lesions

摘要

Despite advances in chemotherapy and radiation therapies, advanced breast cancer still carries a high mortality rate. The need for effective therapies is urgent. The overall aim of this research proposal is to recognize early markers of disease and their interaction with other epidemiological risk factors that can serve as risk indicators for subsequent development of breast cancer from precancerous lesions, and as prognostic markers for progression from primary to metastatic disease. The major histocompatibility complex (MHC) class I molecules are found on the cell membrane of all cells in the body and are involved in intercellular communications and in complex interactions with the immune system. Cancer cells with reduced or aberrant MHC molecules have been shown to evade immune surveillance and become selected for cancer progression and spread of disease to distant sites of the body. About half of all breast cancers have complete loss or reduced level of MHC class I molecules and this finding has been associated with increased tumor invasiveness and more aggressive cancers with poorer outcome. The outlined studies are expected to better define the clinical significance of abnormal MHC class I molecules in precancerous and invasive breast lesions as markers of immunological events that could affect survival, selection, and outgrowth of precancerous cells, and their subsequent progression to breast cancer. These MHC losses could also mark more aggressive tumors and thus contribute to selection of appropriate treatments in individual cases.