Alterations in lipoxygenase and cyclooxygenase-2 catalytic activity and mRNA expression in prostate carcinoma

Recent studies In prostate tissues and especially cell lines have suggested roles for arachidonic acid (AA) metabolizing enzymes in prostate adenocarc inoma (Pea) development or progression. The goal of this study was to more fully characterize lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) gene exp ression and AA metabolism In benign and malignant prostate using snap-froze n tissues obtained intraoperatively and mRNA analyses and enzyme assays. Fo rmation of 15-hydroxyelcosatetraenoic acid (15-HETE) was detected in 23/29 benign samples and 15-LOX-2 mRNA was detected In 21/25 benign samples. In p airs of pure benign and Pea from the same patients, 15-HETE production and 15-LOX-2 mRNA were reduced in Pea versus benign in 9/14 (P = .04) and 14/17 (P = .002), respectively. Under the same conditions, neither 5-HETE nor 12 -HETE formation was detectable in 29 benign and 24 tumor samples; with a mo re sensitive assay, traces were detected in some samples, but there was no clear association with tumor tissue. COX-2 mRNA was detected by nuclease pr otection assay in 7/ 16 benign samples and 5/16 tumors. In benign and tumor pairs from 10 patients, COX-2 was higher in tumor versus benign In only 2, with similar results by in situ hybridization. Paraffin Immunoperoxidase f or COX2 was performed in whole mount sections from 87 additional radical pr ostatectomy specimens, with strong expression in ejaculatory duct as a posi tive control and corroboration with In situ hybridization. No immunostainin g was detected In benign prostate or tumor in 45% of cases. Greater immunos taining in tumor versus benign was present in only 17% of cases, and correl ated with high tumor grade (Gleason score 8 and 9 vs. 5 to 7). In conclusio n, reduced 15-LOX-2 expression and 15-HETE formation Is the most characteri stic alteration of AA metabolism in Pca. Increased 12-HETE and 5-HETE forma tion in Pca were not discernible. Increased COX-2 expression is not a typic al abnormality in Pea in general, but occurs in high-grade tumors.