Estrogen-related receptor (ERR) is a
nuclear receptor that modulates the
estrogen-signaling pathway. Here, we investigated the expression of both ERRbeta and ERRgamma in human prostate tissues. Using original rabbit polyclonal anti-ERRbeta and anti-ERRgamma
antibodies, the expression of ERRbeta and ERRgamma was evaluated by immunohistochemical analysis of cancerous lesions (n = 107) and benign foci (n = 92), obtained by radical
prostatectomy. Stained slides were evaluated for the proportion of immunoreactive cells and their staining intensity. Total immunoreactivity scores (IR scores; range, 0-8) were calculated as the sum of the proportion and intensity scores. The relationship between the clinicopathological characteristics of the patients and the expression of the three ERRs (
ERRalpha,
ERR beta, and ERR gamma) was evaluated. IR scores for ERRbeta and ERRgamma were significantly lower in cancerous lesions than that in benign foci (P < 0.0001, for both). Clinicopathological analyses revealed that the patients with low ERRgamma IR scores (<or=4) tended to show poor
cancer-specific survival (P = 0.07). Then, we used data from our previous study (Fujimura T., Int J
Cancer, 2007; 120: 2325-30). Patients with a high IR score for
ERRalpha and a low score for ERRgamma showed significantly poorer
cancer-specific survival than those with a low IR score for
ERRalpha and a high score for ERRgamma (P = 0.0003). We demonstrated the differential expression of ERRbeta and ERRgamma in prostate tissue. The combined evaluation of the expression of
ERRalpha and ERRgamma could be a significant prognostic factor for
prostate cancer.