Overexpression of NSAID-activated gene product in prostate cancer

NSAID-activated gene (NAG-1) protein was previously identified by microarray analysis as overexpressed in prostate cancer. We performed immunohistochemistry and Western blotting with rabbit polyclonal antibody to NAG-1. Fifty malignant tissues obtained by prostatcctomy and 17 from benign cases were compiled. Cancer tissues included Gleason scores 3-6, 3+4=7, 4+3=7, and 8-10. Cancer and high-grade prostatic intraepithelial neoplasia (PIN) consistently showed moderate to intense cytoplasmic reactivity in 95-100% of epithelium. Staining intensity inversely correlated with preoperative serum prostate-specific antigen (PSA) (p=0.005) and with grade, averaging (on a 0 to 3+ scale) 2.3 +/- 0.6 in the lowest grade group, and 2.0 +/- 0.7, 1.8 +/- 0.5, and 1.5 +/- 0.6 as grade increased (p<0.008). Benign epithelium was nonreactive in 17/17 specimens without concurrent cancer (11 transurethral resection, 2 enucleation, 4 biopsy, p=0.002). Decreased NAG-1 expression in higher grade cancer is consistent with its known antitumorigenic, proapoptotic activities.