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A novel Biomarker in epithelial ovarian cancer

McGrath, Sophie Elena, Annels, Nicola, Madhuri, Thumuluru K, Taylor, Anil, Butler-Manuel, Simon A., Morgan, Richard, Pandha, Hardev and Michael, Agnieszka (2018) A novel Biomarker in epithelial ovarian cancer BMC Cancer, 18, 943.

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EN2 in EOC - BMC 140518 - revised submission.docx - Accepted version Manuscript
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BACKGROUND: Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. METHODS We evaluated 8 Epithelial ovarian cancer cell lines, along with >100 surgical specimens from the Royal Surrey County Hospital (2009-2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/-resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in >150 tumours (immunohistochemistry). RESULTS En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p<0.001), particularly in high-grade serous ovarian cancer (p<0.0001) and in platinum-resistant tumours (p=0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS=28 vs 42 months, p=0.0329; PFS=8 vs 27 months; p=0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p=0.0103). CONCLUSION The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
McGrath, Sophie Elena
Annels, Nicola
Madhuri, Thumuluru K
Taylor, Anil
Butler-Manuel, Simon A.
Date : 3 October 2018
DOI : 10.1186/s12885-018-4816-5
Copyright Disclaimer : © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords : Epithelial ovarian cancer; biomarker; engrailed-2; serous; platinum-resistant
Depositing User : Melanie Hughes
Date Deposited : 13 Nov 2018 11:57
Last Modified : 19 Mar 2019 10:22

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