Expression of estrogen-related receptors in ovarian cancer and impact on survival

• Published in: Journal of cancer research and clinical oncology Vol. 147; no. 9; pp. 2555 - 2567
• Main Authors: Schüler-Toprak, Susanne, Weber, Florian, Skrzypczak, Maciej, Ortmann, Olaf, Treeck, Oliver
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2021; Springer Nature B.V
• Subjects: Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - mortality; Adenocarcinoma, Clear Cell - pathology; Adenocarcinoma, Mucinous - metabolism; Adenocarcinoma, Mucinous - mortality; Adenocarcinoma, Mucinous - pathology; Biomarkers, Tumor - metabolism; Cancer Research; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - mortality; Cystadenocarcinoma, Serous - pathology; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; ERRalpha Estrogen-Related Receptor; Estrogens; Female; Follow-Up Studies; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Oncology; Original Article – Cancer Research; Original – Cancer Research; Ovarian cancer; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Prognosis; Proteins; Receptors, Estrogen - metabolism; Retrospective Studies; Steroid hormone receptors; Survival; Survival Rate; Estrogen-related receptors; Tissue microarray; Overall survival; Progression-free survival; Ovarian cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03673-9

Purpose This study further approaches the role of estrogen-related receptors (ERRs) in ovarian cancer. Protein expression of ERRα, ERRβ and ERRγ in ovarian cancer was assessed and was correlated with ovarian cancer markers, steroid hormone receptors and cancer-associated genes. Additionally, we examined to what extent expression of ERRs affects survival of ovarian cancer patients. Methods For this purpose, we established a tissue microarray from 208 ovarian cancer patients and performed immunohistochemical analyses of the mentioned proteins. Results ERRα and ERRγ protein could be detected at different levels in more than 90% of all ovarian cancer tissues, whereas expression of ERRβ was observed in 82.2% of the cases. ERRα was found to positively correlate with ovarian cancer marker CEA ( p  < 0.005) and ERRγ correlated with ERα ( p  < 0.001). Univariate survival analyses revealed that ERRα expression did not affect overall (OS) or progression-free survival (PFS) of ovarian cancer patients. In contrast, higher expression of ERRβ in serous ovarian cancers was found to lead to a significantly decreased OS ( p  < 0.05). The strongest impact on survival was exhibited by ERRγ. Lower expression of this receptor in women with serous ovarian cancers indicated significantly increased OS compared to those with higher levels of ERRγ ( p  < 0.05). Multivariate survival analyses revealed ERRγ as an independent prognostic marker regarding OS of patients with serous ovarian cancer. Conclusion Our data demonstrating that ERR proteins are frequently expressed in ovarian cancer and high levels of ERRβ and ERRγ significantly decreased OS of serous ovarian cancer patients suggest that these proteins might be interesting therapy targets in this cancer entity.