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Differential Expression of Estrogen Receptor β (ERβ) and Its C-Terminal Truncated Splice Variant ERβcx as Prognostic Predictors in Human Prostatic Cancer

Estrogens have been widely used for the treatment of advanced prostatic adenocarcinoma. However, their direct effect to prostatic cancer cells via estrogen receptors remains unclear. We investigated expression of ERα, wild-type ERβ (wtERβ), and a C-terminal truncated splice variant of ERβ (ERβcx) in 50 benign and 100 malignant human prostatic tissue samples by immunohistochemistry. While strong immunostaining of ERα was consistently identified in the stromal compartment, wtERβ was expressed in epithelial cells in both the benign and malignant foci. However, wtERβ expression was significantly lower in the cancers than in the benign epithelium and inversely correlated with Gleason tumor grade (P < 0.0001 and P = 0.0099, respectively). In contrast, ERβcx was significantly more expressed in the high-grade cancers (83%) compared with the low-grade tumors (22%) and the benign sites (11%) (P < 0.0001, both). Cancer-specific survival of patients with lower wtERβ expression was significantly worse than those with higher expression of wtERβ (P = 0.0018). Conversely, higher ERβcx expression significantly correlated with poor cancer-specific survival (P = 0.0058). These results suggest that differential expressions of wtERβ and ERβcx may be prognostic predictors for prostatic cancer.