Overexpression of ELAV-like Protein HuR is Associated with Increased COX-2 Expression in Atrophy, High-grade Prostatic Intraepithelial Neoplasia, and Incidental Prostate Cancer in Cystoprostatectomies

Background: The human ELAV-like protein HuR regulates the stability of several mRNA targets, including that of cyclooygenase-2 (COX-2). Their expression in prostatic carcinogenesis is uncertain. Objective: To analyze HuR and COX-2 expression in cystoprostatectomies (CyPs) with incidental prostate cancer and compare their expression with those in radical prostatectomies (RPs) with clinically detected cancer. Design, setting, and participants: HuR and COX-2 were immunohistochemically evaluated in normal-looking epithelium (NEp), atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN), and prostate carcinoma (PCa) in 20 CyPs and 20 RPs, both types of specimens with pT2a Gleason score 6 PCa. Measurements: At least 1000 cells were counted in contiguous 400X microscopic fields in each case, separately for NEp, atrophy, HGPIN, and PCa. Results and limitations: There was an increase in the percentage of secretory cells with cytoplasmic HuR staining from NEp to atrophy. HGPIN, and PCa. The mean percentages in NEp, atrophy, and HGPIN adjacent to PCa were greater than away from cancer, both in the CyP and RPs. There was a trend towards a reduced nuclear HuR expression in atrophy, HGPIN. and PCa, compared to NEp. COX-2 staining was seen in the cytoplasm of the basal and secretory cells. There was a reduction in the mean Proportion of positive basal cells and progressive increase in the percentage of positive secretory cells from atrophy to HGPIN and PCa, compared to NEp. Cytoplasmic HuR overexpression was correlated with COX-2 expression. There was no difference in HuR and COX-2 expression between cancers with tumour volume <0.5 ccm or >0.5 ccm. The limitations of this study were the small number of cases investigated and lack of a control group without cancer. Conclusions: The secretory cells showed shift in HuR staining from nuclear in NEp to cytoplasmic in PCa. This is associated with a parallel shift in COX-2 expression from basal to secretory cells. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.