Prognostic relevance of EP3-receptor expression in sporadic breast cancer tissue

Aim: The prostaglandin EP3 receptor is one of four membrane bound receptors (EP1 – 4) identified for prostaglandin E2. Prostaglandins have a variety of biological effects; however, elevated prostaglandin synthesis has also been associated with the development of different kinds of cancer. The involvement of EP1 – 4-receptors in carcinogenesis has been suggested. Furthermore, EP3 is known to regulate the uPA/PAI-1 pathway. This analysis evaluates the expression of EP3-receptor on breast cancer tissue and its correlation to recurrence and survival.

Material and methods: A total of 320 sporadic breast cancer tissue samples (consecutive sampling) were analyzed for EP3-expression by immunhistochemistry. Tissue was stained with primary anti-EP3-antibodies (rabbit IgG); immunoreactivity was quantified by the semi-quantitative IR-score. Statistical analyses were performed with SPSS, Kaplan-Meier-estimates were used for survival analyses.

Results: EP3-receptor was expressed on 88% of all cases. EP3-receptor expression significantly correlated with longer recurrence free survival (p < 0.001) as well as overall survival (p < 0.001). EP3-receptor expression did not correlate with the expression of estrogen receptors.

Summary: The correlation of EP3-receptor expression with improved recurrence free and overall survival in sporadic breast cancer is especially interesting as EP3 is known to regulate uPA and PAI-1. uPA and PAI-1 are two well-known predictive markers associated with unfavourable survival in breast cancer. Therefore the EP3-receptor might be a possible target for future anti-tumor therapy. Ongoing studies by our group aim to further examine the correlation of EP3-receptor and PAI-1 expression and their relevance in the clinical course and outcome of breast cancer.