Differential expression of estrogen-related receptors β and γ (ERRβ and ERRγ) and their clinical significance in human prostate cancer

Estrogen-related receptor (ERR) is a nuclear receptor that modulates the estrogen-signaling pathway. Here, we investigated the expression of both ERR beta and ERR gamma in human prostate tissues. Using original rabbit polyclonal anti-ERR beta and anti-ERR gamma antibodies, the expression of ERR beta and ERR gamma 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 (ERR alpha, ERR beta, and ERR gamma) was evaluated. IR scores for ERR beta and ERR gamma were significantly lower in cancerous lesions than that in benign foci (P < 0.0001, for both). Clinicopathological analyses revealed that the patients with low ERR gamma IR scores (<= 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 ERR alpha and a low score for ERR gamma showed significantly poorer cancer-specific survival than those with a low IR score for ERR alpha and a high score for ERR gamma (P = 0.0003). We demonstrated the differential expression of ERR beta and ERR gamma in prostate tissue. The combined evaluation of the expression of ERR alpha and ERR gamma could be a significant prognostic factor for prostate cancer. (Cancer Sci 2010; 101: 646-651)