Vol.:(0123456789) 1 3
Journal of Cancer Research and Clinical Oncology
https://doi.org/10.1007/s00432-018-2785-3
ORIGINAL ARTICLE – CANCER RESEARCH
The role of EP3-receptor expression in cervical dysplasia
Anna Hester
1
· Manuel Ritzer
1
· Christina Kuhn
1
· Elisa Schmoeckel
2
· Doris Mayr
2
· Thomas Kolben
1
·
Christian Dannecker
1
· Sven Mahner
1
· Udo Jeschke
1
· Theresa Maria Kolben
1
Received: 9 October 2018 / Accepted: 27 October 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
Purpose Prostaglandin-mediated infammatory reactions play a major role in diferent cancers. Prostaglandin E2-receptor
3 (EP3) expression correlates with FIGO stages in cervical cancer and has been shown to be an independent prognostic fac-
tor 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 signifcantly correlated with diferent 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 sig-
nifcantly 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 signifcantly 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 fndings support the importance of the prostanoid pathway in cervical cancer and could help to identify
targets for future therapies.
Keywords EP-receptor · EP3 · Prostaglandin E2 · CIN · Cervical intraepithelial neoplasia · Cervical cancer
* Udo Jeschke
udo.jeschke@med.uni-muenchen.de
Anna Hester
anna.hester@med.uni-muenchen.de
Manuel Ritzer
ritzer.manuel@gmx.de
Christina Kuhn
christina.kuhn@med.uni-muenchen.de
Elisa Schmoeckel
elisa.schmoeckel@med.uni-muenchen.de
Doris Mayr
doris.mayr@med.uni-muenchen.de
Thomas Kolben
thomas.kolben@med.uni-muenchen.de
Christian Dannecker
christian.dannecker@med.uni-muenchen.de
Sven Mahner
sven.mahner@med.uni-muenchen.de
Theresa Maria Kolben
theresa.kolben@med.uni-muenchen.de
1
Department of Obstetrics and Gynecology, University
Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich,
Germany
2
Department of Pathology, LMU Munich, Thalkirchnerstrasse
36, 80337 Munich, Germany