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Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer
McGrath, S.E. Annels, N. Madhuri, T.K. Tailor, A. Butler-Manuel, S.A. Morgan, Richard Pandha, H. Michael, A.
McGrath, S.E.
Annels, N.
Madhuri, T.K.
Tailor, A.
Butler-Manuel, S.A.
Morgan, Richard
Pandha, H.
Michael, A.
Publication Date
2018-10
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© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), 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 (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Open Access status
openAccess
Accepted for publication
2018-09-13
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Abstract
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.
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Citation
McGrath SE, Annels N, Madhuri TK et al (2018) Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer. BMC Cancer. 18: 943.
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Article