Phospholipid Hydroperoxide Gluthatione Peroxidase Overexpression Is Associated With A Poor Overall Survival In Human Breast Cancer.

635 Background: Phospholipid Hydroperoxide Glutathione Peroxidase (PH-GPx or GPx4) is an essential antioxidant protein with potential implications in cell proliferation and apoptosis: it is the only known enzyme able to reduce lipid peroxides directly in cell membranes. Although lipid peroxidation is a common mechanism for antitumoral drug activity, it has not been studied in the carcinogenic context. Methods: The aim of this study was to evaluate the relative expression of PH-GPx in samples of human breast invasive ductal carcinoma from 96 patients with stage I-II disease. Median age was 57 years (range 27–80). Forty eight patients had lymph-node negative and 48 lymph-node positive disease. Quantitative RT-PCR amplifications of PH-GPx were performed with TaqMan Gene Expression Assays products. Laboratory results were correlated with data retrospectively obtained from the patients’ clinical record. SPSS software was used for statistics. Results: Overexpression of PH-GPx was significantly associated with a poor overall survival in the whole group of 96 patients (p 0.032). The relative weight of this gene in determining survival was higher than that of single genes included in a 70-gene expression profile. PH-GPx overexpression was also correlated with the grade of differentiation. Conclusions: PH-GPx overexpression carries a poor prognosis in patients with breast cancer. Our results suggest that PH-GPx expression may be needed to control the redox status in breast tissues. Additional studies are needed to evaluate the functional implications of PH-GPx in breast carcinogenesis. No significant financial relationships to disclose.