Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis

BACKGROUND. Cancer patients produce autoantibodies to self-proteins called tumor-associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS. Serum autoantibodies to the survival protein lens epithelium-derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting. RESULTS. Anti-LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P < 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells. CONCLUSIONS. The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients. (C) 2004 Wiley-Liss, Inc.