EP3 (prostaglandin E2 receptor 3) expression is a prognostic factor for progression-free and overall survival in sporadic breast cancer.

Abstract

BACKGROUND:

In various cancers, overexpression of cyclooxygenase (COX)-2 and elevated prostaglandin (PG) E2 synthesis have been associated with tumor development and progression. The potential of COX-2 inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions are analyzed in current research in search for targeted anti-PG therapies. EP2 and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast cancer, is not yet clear and both pro- and anti-tumorigenic effects have been described. Our study evaluates EP3 receptor expression in sporadic breast cancer and its association with clinicopathological parameters, progression-free and overall survival.

METHODS:

Two hundred eighty-nine sporadic breast cancer samples without primary distant metastasis were immunohistochemically analyzed for EP3 receptor expression. Tissue was stained with primary anti-EP3-antibodies. Immunoreactivity was quantified by the immunoreactivity-score (IRS); samples with an IRS ≥ 2 scored as EP3 positive. Chi-squared and Mann-Whitney-U test were used for comparison of data; Kaplan-Meier estimates and Cox-regression were used for survival analyses.

RESULTS:

EP3 receptor was expressed in 205 of 289 samples analyzed (70.9%). EP3 receptor expression was not associated with clinicopathological parameters (e. g. tumor size, hormone receptors, lymph node status). Kaplan-Meier estimates showed a significant association of EP3 positivity with improved progression-free survival (p = 0.002) and improved overall survival (p = 0.001) after up to 10 years. Cox regression analysis confirmed EP3 positivity as a significant prognostic factor even when other known prognosticators were accounted for.

CONCLUSIONS:

In sporadic breast cancer, EP3 receptor expression is not significantly associated with clinicopathological parameters but is a significant prognostic factor for improved progression-free and overall survival. However, the functional aspects of EP3 receptor in breast cancer and the way how EP3 may oppose the pro-tumorigenic effects of PGE2 elevation and COX-2 overexpression are not fully understood so far. Further studies aiming at identification of the factors regulated by EP3 are necessary to evaluate the possibility of targeting EP3 in future anti-tumor therapy in breast cancer.

• Authors: Anna Semmlinger, Viktoria von Schoenfeldt, Verena Wolf, Alexandra Meuter, Theresa Maria Kolben, Thomas Kolben, Christine Zeder-Goess, Florian Weis, Julia Gallwas, Rachel Wuerstlein, Kerstin Hermelink, Elisa Schmoeckel, Nadia Harbeck, Doris Mayr, Sven Mahner, Udo Jeschke, Nina Ditsch
• Journal: BMC cancer (BMC Cancer) Vol. 18 Issue 1 Pg. 431 (04 16 2018) ISSN: 1471-2407 [Electronic] England
• PMID: 29661238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase 2 Inhibitors
• PTGER3 protein, human
• Receptors, Prostaglandin E, EP3 Subtype
• Dinoprostone

Topics

• Aged
• Animals
• Breast Neoplasms (drug therapy, genetics, pathology)
• Carcinogenesis (genetics)
• Cyclooxygenase 2 Inhibitors (administration & dosage)
• Dinoprostone (administration & dosage)
• Disease Progression
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Prognosis
• Receptors, Prostaglandin E, EP3 Subtype (genetics)