Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: Correlation with grade and expression in high-grade prostatic intraepithelial neoplasia

Arachidonic acid (AA) metabolites are implicated in the oncogenesis:bf seve ral tumors, including prostate cancer. 15-Lipoxygenase-2 (15-LOX-2) is a no vel AA-metabolizing enzyme with a limited tissue distribution, which includ es prostate, lung, skin, and cornea, Previous studies have shown that 15-LO X-2 is present: in benign prostate secretory cells and reduced in prostate adenocarcinoma and that production of the 15-LOX-2 metabolite 15S-hydroxyei cosatetraenoic acid is reduced in malignant compared with benign prostate. The objective of this study was to determine the frequency with which 15-LO X-2 immunostaining is reduced in prostate carcinoma and to correlate reduce d expression with tumor differentiation (grade) and other pathologic parame ters in radical prostatectomy specimens. Paraffin immunoperoxidase with a p olyclonal antibody specific for 15-LOX-2 was performed on tumors and benign portions from 70 cases, and the percentage of tumor immunostaining for 15- LOX-2 was assessed. Whereas uniform 15-LOX-2 immunostaining was observed in secretory cells of benign glands, it was markedly reduced or absent in mos t adenocarcinomas: 23 of 70 tumors showed completely absent 15-LOX-2 immuno staining, and 45 of 70 cases showed negative immunostaining in more than 50 % of the tumor, The extent of reduced 15-LOX-2 immunostaining correlated wi th tumor differentiation, with retained expression particularly in Gleason score 5 tumors versus a significant reduction of 15-LOX-2 in higher-grade t umors (mean a: SD tumor 15-LOX-2 positive: Gleason score 5 = 67% +/- 30%, G leason score 6 = 16% +/- 30%, Gleason score 7 = 23% +/- 28%, Gleason score greater than or equal to 8 = 41% +/- 46%). In 16 cases with multifocal tumo rs or different foci of the same tumor with different grades, the higher-gr ade foci had significantly reduced 15-LOX-2 expression compared with the lo wer-grade foci. In peripheral zone tumors without complete loss of 15-LOX-2 expression, there was a significant inverse relationship between 15-LOX-2 immunostaining and tumor volume. There was not a significant correlation be tween 15-LOX-2 immunostaining and serum PSA or pathologic stage. In a subse t of 27 cases, 15-LOX-2 expression in high-grade prostatic intraepithelial neoplasia (HGPIN) glands was significantly reduced compared with benign gla nds. These data show that in contrast to the uniform expression of 15-LOX-2 in differentiated secretory cells of benign prostate, reduced 15-LOX-2 is a common alteration in prostate carcinoma, and this correlates with tumor c ell differentiation. That reduced expression is seen in HGPIN suggests that this may be an early alteration in carcinoma development. Copyright (C) 20 00 by W.B. Saunders Company.