Decreased expression of stromal estrogen receptor α and β in prostate cancer

Background: Recently there has been an increased interest in the role of tumor-associated stroma in prostate tumorigenesis, but little is known about the respective roles of stomal ERα and ERβ in prostate cancer (PCa). This study characterizes the expression patterns of ERα and ERβ in tumor-associated stroma in association with various clinicopathological factors of importance in PCa prognosis and treatment. Design: Immunohistochemistry was performed using antibodies against ERα and ERβ to characterize their expression patterns in PCa tissue. Stromal ER levels (ERα and ERβ) on tissue sections (n=47), were compared between tumor associated stroma and adjacent benign associated stroma. Immunohistochemistry was also performed on a PCa tissue microarray (TMA) (n=177) to correlate stromal expression with various clinicopathological parameters. The levels of ER nuclear expression were scored semi-quantitatively. Results: The expression levels of both ERα and ERβ were significantly lower in tumor-associated stroma than stroma surrounding benign prostatic glands on the same tissue section (ERα: p<0.01; ERβ: p=0.01). When correlated with clinicopathological factors, the level of ERα expression in tumor-associated stroma showed a positive correlation with Gleason score (R²=0.8638). The expression of ERα was higher in PCa with advanced tumor stage (p=0.05) and not significantly different in extraprostatic extension (p>0.05). The level of ERβ expression in tumor-associated stroma was decreased in patients older than 60 years compared to younger patients (p=0.01). Conclusion: This study demonstrates significant down-regulation of ERα and ERβ expression in the tumor-associated stroma of PCa. However, the level of ERα expression in tumor-associated stroma shows a positive correlation with cancer differentiation and tumor stage.