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

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