Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Obstet Gynecol. Feb 10, 2016; 5(1): 118-126
Published online Feb 10, 2016. doi: 10.5317/wjog.v5.i1.118
Alpha1B adrenoceptor expression is a marker of reduced survival and increased tumor recurrence in patients with endometrioid ovarian cancer
Dascha Deutsch, Suha Deen, Frank Entschladen, Clare Coveney, Robert Rees, Kurt S Zänker, Desmond George Powe
Dascha Deutsch, Frank Entschladen, Kurt S Zänker, Institute of Immunology, University of Witten/Herdecke, DE-58448 Witten, Germany
Suha Deen, Desmond George Powe, Department of Cellular Pathology, Queens Medical Centre, Nottingham University Hospitals Trust, Nottingham NG7 2UH, United Kingdom
Clare Coveney, Robert Rees, Desmond George Powe, the John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham NG11 8NS, United Kingdom
Author contributions: Powe DG contributed to study concept and design, acquisition and analysis of data, data interpretation and manuscript production; Deutsch D contributed to acquisition and analysis of data, data interpretation and manuscript production, laboratory experiments; Deen S contributed to supply of tissue samples and clinical data; Entschladen F contributed to study concept and manuscript production; Coveney C contributed to laboratory experiments; Rees R and Zänker KS contributed to project management.
Supported by Financial support from the Fritz Bender Foundation (Munich; to Dascha Deutsch, Frank Entschladen and Kurt S Zänker); from the Nottingham University Hospital Trustees (contributed to the reagent costs).
Institutional review board statement: This study was approved by the Derbyshire ethics committee (reference 07/H0401/156) and Department of Research and Innovation, Queens Medical Centre, Nottingham University Hospitals Trust, Nottingham NG7 2UH, United Kingdom.
Institutional animal care and use committee statement: No animals were used in this study.
Conflict-of-interest statement: The authors have declared no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Desmond George Powe, PhD, Principal Healthcare Research Scientist, Department of Cellular Pathology, Queens Medical Centre, Nottingham University Hospitals Trust, Derby Road, Nottingham NG7 2UH, United Kingdom. des.powe@nottingham.ac.uk
Telephone: +44-115-9249924-63484 Fax: +44-115-9709759
Received: April 24, 2015
Peer-review started: April 29, 2015
First decision: June 9, 2015
Revised: October 14, 2015
Accepted: November 10, 2015
Article in press: November 11, 2015
Published online: February 10, 2016
Abstract

AIM: To investigate the expression patterns of different adrenoceptor isoforms in ovarian cancer and their association with survival and tumor recurrence.

METHODS: The protein expression levels of α1B, α2C and β2 adrenoceptor were assessed in unselected ovarian cancer using immunohistochemistry on microarrayed archival tissue samples. A database containing clinical and pathology parameters and follow-up was used to investigate the association between adrenoceptor isoform expression with ovarian specific survival and tumor recurrence, using univariate and multivariate statistical analysis.

RESULTS: Expression of α1B showed an association with reduced ovarian specific survival (P = 0.05; CI: 1.00-1.49) and increased tumor recurrence (P = 0.021, CI: 1.04-1.69) in the whole patient group. On sub-analysis the expression of α1B in endometrioid cancers (χ2 = 5.867, P = 0.015) was found to predict reduced ovarian specific survival and increased tumor recurrence independently of tumor grade, clinical stage and chemotherapy. An association with clinical outcome was not seen for α2C or β2 AR.

CONCLUSION: Alpha1B adrenoceptor protein was found to predict increased risk of tumor recurrence and reduced mortality in patients with endometrioid type ovarian cancer and should be investigated as a biomarker for identifying patients at increased risk of disease progression. Furthermore, α adrenergic receptor antagonists with α1B selectivity should be investigated as a possible adjuvant therapy for treating patients with endometrioid cancer. Proof of principle could be tested in a retrospective population study.

Keywords: Alpha adrenoceptor, Beta adrenoceptor, β-blockers, α-blockers, Ovarian cancer, Prognosis, Cancer therapy

Core tip: Epidemiological studies suggest that β-blockers might have a role in reducing metastatic spread and tumor recurrence and thereby prolong patient survival in some cancer types. In this novel study we found α1B adrenoceptor is a biomarker of tumor recurrence in endometrioid ovarian cancer. Further studies are needed to test if selective α1 adrenergic receptor antagonists inhibit tumor recurrence and prolong survival in patients with this type of cancer.