EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer.

COX-2 EP4 PGE2 cancer survival prognosis vulvar carcinoma

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
19 Mar 2021
Historique:
received: 07 01 2021
revised: 01 03 2021
accepted: 17 03 2021
entrez: 3 4 2021
pubmed: 4 4 2021
medline: 4 4 2021
Statut: epublish

Résumé

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients' survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2'-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (

Identifiants

pubmed: 33808776
pii: cancers13061410
doi: 10.3390/cancers13061410
pmc: PMC8003514
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Friedrich-Baur-Stiftung
ID : 33/19

Références

Cancers (Basel). 2019 Oct 18;11(10):
pubmed: 31635323
Pharmacol Rev. 2013 Jun 17;65(3):1010-52
pubmed: 23776144
Cell Death Dis. 2016 Mar 24;7:e2154
pubmed: 27010855
Oncogene. 2010 Feb 11;29(6):781-8
pubmed: 19946329
Br J Cancer. 2001 Sep 28;85(7):1023-31
pubmed: 11592775
J Cancer Res Clin Oncol. 2020 Mar;146(3):569-577
pubmed: 32025868
Breast Cancer Res. 2007;9(4):210
pubmed: 17640394
J Biol Chem. 2002 Nov 15;277(46):44147-54
pubmed: 12215436
Int J Gynecol Cancer. 2009 May;19(4):756-60
pubmed: 19509584
Int J Mol Sci. 2018 Mar 29;19(4):
pubmed: 29596308
Nat Rev Cancer. 2001 Oct;1(1):11-21
pubmed: 11900248
Eur J Cancer. 2013 Nov;49(16):3450-61
pubmed: 23886586
BMC Cancer. 2016 Jul 13;16:465
pubmed: 27411473
J Biol Chem. 2004 Nov 5;279(45):46700-5
pubmed: 15347673
Pharmacol Ther. 2013 Jun;138(3):485-502
pubmed: 23523686
JAMA. 2001 Aug 22-29;286(8):954-9
pubmed: 11509060
J Low Genit Tract Dis. 2007 Apr;11(2):80-5
pubmed: 17415111
Am J Pathol. 1998 Dec;153(6):1741-8
pubmed: 9846965
Gynecol Oncol. 2004 Feb;92(2):537-44
pubmed: 14766245
Trends Immunol. 2012 Mar;33(3):119-26
pubmed: 22277903
Int J Mol Sci. 2017 Jul 19;18(7):
pubmed: 28753926
Tumour Biol. 2016 Sep;37(9):12203-12211
pubmed: 27230680
Am J Surg Pathol. 2001 Jul;25(7):884-91
pubmed: 11420459
Lancet Oncol. 2012 Jun;13(6):607-15
pubmed: 22575588
Hum Pathol. 2004 Dec;35(12):1477-83
pubmed: 15619206
Mod Pathol. 2017 Apr;30(4):549-562
pubmed: 28059099
Cancer Res. 2006 Mar 15;66(6):2923-7
pubmed: 16540639
Int J Gynaecol Obstet. 2018 Oct;143 Suppl 2:4-13
pubmed: 30306583
Int J Cancer. 2017 Dec 1;141(11):2174-2186
pubmed: 28730615
Anticancer Res. 2009 Feb;29(2):545-52
pubmed: 19331201
Carcinogenesis. 2009 Jan;30(1):141-9
pubmed: 18849297
Hum Pathol. 1998 Sep;29(9):932-48
pubmed: 9744309
J Invest Dermatol. 2002 Nov;119(5):1027-33
pubmed: 12445188
Int J Cancer. 2017 Mar 1;140(5):1186-1198
pubmed: 27859245
Oncotarget. 2016 Dec 27;7(52):86730-86739
pubmed: 27893418
Hum Pathol. 2017 Aug;66:144-151
pubmed: 28705710
Nat Rev Cancer. 2010 Mar;10(3):181-93
pubmed: 20168319
Physiol Rev. 1999 Oct;79(4):1193-226
pubmed: 10508233
Oncol Lett. 2018 Jan;15(1):552-558
pubmed: 29285200
Arch Gynecol Obstet. 2020 Jun;301(6):1365-1375
pubmed: 32363546
Exp Cell Res. 2007 Aug 15;313(14):2969-79
pubmed: 17631291
Nat Rev Cancer. 2010 Aug;10(8):550-60
pubmed: 20592731
Oncotarget. 2017 Sep 22;8(52):89802-89810
pubmed: 29163789
Gynecol Oncol. 2019 Aug;154(2):280-282
pubmed: 31248667
Oncogene. 1999 Dec 20;18(55):7908-16
pubmed: 10630643
Br J Pharmacol. 2015 Nov;172(22):5239-50
pubmed: 26377664
Pathologe. 1987 May;8(3):138-40
pubmed: 3303008
Cells. 2020 May 15;9(5):
pubmed: 32429133
Expert Rev Anticancer Ther. 2015 Jun;15(6):629-37
pubmed: 25997120
Front Immunol. 2014 Mar 26;5:127
pubmed: 24723924

Auteurs

Anna Buchholz (A)

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

Aurelia Vattai (A)

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

Sophie Fürst (S)

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

Theresa Vilsmaier (T)

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

Christina Kuhn (C)

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany.

Elisa Schmoeckel (E)

Department of Pathology, LMU Munich, Thalkirchner Str. 142, 80337 Munich, Germany.

Doris Mayr (D)

Department of Pathology, LMU Munich, Thalkirchner Str. 142, 80337 Munich, Germany.

Christian Dannecker (C)

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany.

Sven Mahner (S)

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

Udo Jeschke (U)

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany.

Helene H Heidegger (HH)

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

Classifications MeSH