Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.The multistep model of human breast cancer progression suggests that invasive breast cancer (IBC) develops in a stepwise manner from premalignant hyperplasia to ductal carcinoma in situ (DCIS) to metastatic carcinoma [1]. Benign hyperplasia (BH), which involves the proliferation of epithelial cells, commonly develops with aging and may increase the risk of breast cancer [2]. DCIS, the most common non-invasive form of breast cancer, is an abnormal proliferation of epithelial cells confined to the ducts. However, 1-2% of DCIS patients progress to IBC as cells begin to invade the basement membrane. Once the basement membrane has been breached, cells can migrate from the primary tumor through the blood stream to secondary sites where the cells colonize. Metastatic cancer is the leading cause of cancer-related morbidity and mortality [3,4].It has been suggested that aging results from exposure of cellular macromolecules to reactive oxygen species (ROS) and that accumulation of ROS-induced damage is responsible for the development of diseases associated with aging, including cancer [5-9]. Oxidative stress response proteins are needed to prevent the accumulation of ROS, which include superoxide, hydrogen peroxide and hydroxy radical. Cu/Zn superoxide dismuta