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 prostatectomy 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 (1 transurethral resection, 2 enucleation, 4 biopsy, p=0.002). Decreased NAG I expression in higher grade cancer is consistent with its known antitumorigenic, proapoptotic activities
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