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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Engrailed-2 (EN2) – a novel biomarker in epithelial ovarian cancer

Authors: Sophie Elena McGrath, Nicola Annels, Thumuluru K. Madhuri, Anil Tailor, Simon A. Butler-Manuel, Richard Morgan, Hardev Pandha, Agnieszka Michael

Published in: BMC Cancer | Issue 1/2018

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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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Metadata
Title
Engrailed-2 (EN2) – a novel biomarker in epithelial ovarian cancer
Authors
Sophie Elena McGrath
Nicola Annels
Thumuluru K. Madhuri
Anil Tailor
Simon A. Butler-Manuel
Richard Morgan
Hardev Pandha
Agnieszka Michael
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4816-5

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