Abstract
Purpose
Prostaglandin-mediated inflammatory reactions play a major role in different cancers. Prostaglandin E2-receptor 3 (EP3) expression correlates with FIGO stages in cervical cancer and has been shown to be an independent prognostic factor for overall survival. EP3 expression levels in cervical intraepithelial neoplasia (CIN) as the precursor lesion of cervical cancer are currently unknown.
Methods
EP3 expression was analyzed by immunohistochemistry in 124 patient samples (CIN 1–3 and healthy controls) using the IR-scoring system. Expression levels were correlated with clinical outcome to assess for prognostic relevance in patients with CIN 2. Data analysis was performed using Kruskal–Wallis and Mann–Whitney U test.
Results
EP3 expression levels significantly correlated with different grades of cervical dysplasia. Median EP3-IRS in healthy cervical tissue was 12 (n = 13) compared to 9 in CIN 1 (n = 38; p = 0.031 vs. healthy control), 6 in CIN 2 (n = 45; p < 0.001 vs. CIN 1) and 4 in CIN 3 (n = 28, p = 0.008 vs. CIN 2). The percentage of EP3 expressing cells in CIN 2 lesions was significantly lower in progressive than in regressive cases (mean percentage of EP3 positive cells in progress: 3.8%, n = 18; in regress: 9.3%, n = 20; p = 0.040).
Conclusion
EP3 expression significantly decreases with higher grades of cervical intraepithelial neoplasia—which is in line with published IR scores in cervical cancer patients—and seems to be a prognostic marker for regression or progression of CIN 2 lesions. Our findings support the importance of the prostanoid pathway in cervical cancer and could help to identify targets for future therapies.
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This study was financially supported by Heuer-Foundation.
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A. H. has received research Grants from the “Walter Schulz Stiftung” and a speaker and advisory board honorarium from Roche, Germany. T. M. K. is employed at Roche at the time of manuscript submission. S. M. received research support, advisory board, honoraria and travel expenses from AstraZeneca, Clovis, Medac, MSD, PharmaMar, Roche, Sensor Kinesis, Tesaro and Teva. All other authors declare that they have no conflict of interest.
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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 (167-14).
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Informed consent was obtained from all individual participants included in the study.
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The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
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Hester, A., Ritzer, M., Kuhn, C. et al. The role of EP3-receptor expression in cervical dysplasia. J Cancer Res Clin Oncol 145, 313–319 (2019). https://doi.org/10.1007/s00432-018-2785-3
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DOI: https://doi.org/10.1007/s00432-018-2785-3