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EP3 receptor is a prognostic factor in TA-MUC1-negative ovarian cancer

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Prostaglandin-mediated inflammatory reactions play a major role in different cancers. Recently, it has been observed that prostaglandin E2-receptor 3 (EP3) might be an independent prognostic factor for overall survival in cervical and endometrial cancer. The role of EP3 expression in ovarian cancer is currently unknown.

Methods

EP3 expression was analyzed by immunohistochemistry in 156 patient samples using the IR-scoring system. Expression levels were correlated with clinical and pathological parameters and with overall survival (OS) to assess for prognostic relevance. Data analysis was performed using Spearman’s correlations, Kruskal–Wallis test and Kaplan–Meier estimates.

Results

EP3 expression was significantly higher in clear-cell carcinoma (p < 0.001) compared to the other histological subtypes. No further correlations with clinical parameters could be found. EP3 expression correlated significantly with FSH-receptor expression (p < 0.001), galectin-1 expression in the tumor (p = 0.012) and with cytoplasmatic TA-MUC1 expression (p = 0.001). None of these parameters showed significant correlation with OS. In the TA-MUC1 negative subgroup, EP3 negative patients showed significantly longer OS (median OS: 102 months vs. 34 months in EP3 positive patients, p = 0.035), while EP3 did not appear to have prognostic relevance in the TA-MUC1-positive subgroup.

Conclusion

The potential prognostic relevance of EP3 expression for OS in TA-MUC1 negative patients might reflect an interplay between the COX and the MUC1 pathway, as it has been shown that MUC1 could induce COX2 expression. Our findings support the importance of the prostanoid signaling in TA-MUC1 negative ovarian cancer; however, future studies are necessary to characterize specific pathways and possible interactions.

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Data availability

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by laboratory resources.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany

    Bastian Czogalla, Christina Kuhn, Sabine Heublein, Thomas Kolben, Fabian Trillsch, Alexander Burges, Sven Mahner, Udo Jeschke & Anna Hester

  2. Department of Gynecology and Obstetrics, University of Heidelberg, 69120, Heidelberg, Germany

    Sabine Heublein

  3. Department of Pathology, Ludwig-Maximilians University of Munich, 81337, Munich, Germany

    Elisa Schmöckel & Doris Mayr

Authors
  1. Bastian Czogalla
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  2. Christina Kuhn
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  3. Sabine Heublein
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  4. Elisa Schmöckel
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  5. Doris Mayr
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  6. Thomas Kolben
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  7. Fabian Trillsch
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  8. Alexander Burges
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  9. Sven Mahner
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  10. Udo Jeschke
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  11. Anna Hester
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Corresponding author

Correspondence to Udo Jeschke.

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Conflict of interest

A.H. has received research grants from the “Walter Schulz Stiftung” and honoraria from Roche and Pfizer. S.M. received research support, advisory board, honoraria and travel expenses from AstraZeneca, Clovis, Medac, MSD, PharmaMar, Roche, Sensor Kinesis, Tesaro and Teva. F.T. declares research support, advisory board, honoraria and travel expenses from AstraZeneca, Medac, PharmaMar, Roche, and Tesaro. S.H. reports grants from Baden-Württemberg Ministry of Science, Research and the Arts, from StuRa Ruprecht-Karls-University of Heidelberg, FöFoLe LMU Munich Medical Faculty, grants from FERRING, personal fees from Roche, other from Astra Zeneca, grants from Novartis Oncology, grants and non-financial support from Apceth GmbH, non-financial support from Addex and grants from Heuer Stiftung. She further reports grants from Deutsche Forschungsgemeinschaft within the funding program Open Access Publishing, by the Baden-Württemberg Ministry of Science, Research and the Arts and by Ruprecht-Karls-University Heidelberg, outside the submitted work. All other authors declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The current study was approved by the Ethics Committee of the Ludwig-Maximilians-University, Munich, Germany (approval number 227-09 and 18-392).

Informed consent

This study used tumor tissue that had initially been collected for histo-pathological diagnostics. At the time, the tissue was examined for the current study, all diagnostic procedures had already been fully completed, and the tissue used was thus classified as left-over material. All patient data were fully anonymized, the Ethics Committee of the Ludwig-Maximilians-University (Munich, Germany) approved the study (227-09 and 18-392), and the study was performed according to the standards set in the Declaration of Helsinki 1975. As per declaration of our ethics committee, no written informed consent of the participants or permission to publish is needed given the circumstances described above. Researchers were blinded from patient data during experimental and statistical analyses.

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Czogalla, B., Kuhn, C., Heublein, S. et al. EP3 receptor is a prognostic factor in TA-MUC1-negative ovarian cancer. J Cancer Res Clin Oncol 145, 2519–2527 (2019). https://doi.org/10.1007/s00432-019-03017-8

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  • DOI: https://doi.org/10.1007/s00432-019-03017-8

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