Increased expression of estrogen-related receptor a (ERRa) is a negative prognostic predictor in human prostate cancer

The nuclear receptor ERRa (estrogen-related receptor a) isknown to modulate the estrogen-signaling pathway, but the biologicalsignificance of ERRa in the prostate remains unclear. Weinvestigated the expression of ERRa in human prostate tissuesand cancer cell lines to evaluate the potential roles of the receptorin prostate cancer (PC). Western blot analysis of ERRa was performedin three cell lines of human PC (LNCaP, DU145 and PC-3). The expressions of ERRa in cancerous lesions (n 5 106) andbenign foci (n 5 99) of 106 surgically obtained prostate specimenswere evaluated by immunohistochemistry. The relationshipsbetween the ERRa expression and clinicopathological featureswere evaluated. Western blot analysis using the polyclonal anti-ERRa antibody detected a 52 kD band in all three PC cell lines.Positive immunostaining of ERRa in the nuclei was found in 73(69%) cancerous and 47 (47.5%) benign epithelium, whereas thestromal tissues were negative for ERRa. The mean immunoreactivityscore (IR score) of the cancerous lesions (3.5 6 2.6) was significantlyhigher than that of the benign foci (1.8 6 2.1) (p <0.0001). The IR score of the cancerous lesions significantly correlatedwith the Gleason score (p 5 0.0135). Univariate and multivariatehazard analyses revealed significant correlations betweenelevated ERRa expression and poor cancer-specific survival (p 50.0141 and 0.0367, respectively). The enhanced expression ofERRa might play a role in the development of human PC andserve as a significant prognostic factor for the disease.' 2007 Wiley-Liss, Inc.