Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker

Richard Morgan, Richard T Bryan, Saqib Javed, Francesca Launchbury, Maurice P Zeegers, K K Cheng, Nicholas D James, D Michael A Wallace, Carolyn D Hurst, Douglas G Ward, Margaret A Knowles, Hardev Pandha

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33 Citations (Scopus)


Despite significant advances in our understanding of the molecular pathology of bladder cancer, it remains a significant health problem with high morbidity and mortality associated with muscle-invasive bladder cancer (stages T2+), and high costs associated with the surveillance of non-muscle-invasive bladder cancer (NMIBC, stages Ta/T1/Tis). Moreover, current diagnostic biomarkers are suboptimal and of poor utility for low grade disease and surveillance. In this study, we show that the Engrailed-2 (EN2) transcription factor is expressed in, and secreted by, bladder cancer cell lines and patient tumour specimens, justifying an evaluation of urinary EN2 as a diagnostic biomarker in bladder cancer using archived samples from an established biospecimen collection. In patients with NMIBC, urinary EN2 was detected in most cases with an overall sensitivity of 82% and specificity of 75%. The sensitivity for stage Ta and T1 tumours was 71% and 76%, respectively, and 94% for stage T2+ tumours. This compares favourably with existing markers. The sensitivity for tumour grades 1, 2 and 3 was 69%, 78% and 87%, respectively. Thus urinary EN2 has the potential to be a more sensitive and specific protein biomarker for NMIBC than currently available tests.
Original languageEnglish
Pages (from-to)2214-2222
Number of pages9
JournalEuropean Journal of Cancer
Issue number9
Publication statusPublished - 21 Feb 2013

Bibliographical note

Copyright © 2013 Elsevier Ltd. All rights reserved. Publication date on PubMed shown as June 2013.


  • Bladder cancer
  • Diagnostic
  • Biomarker
  • EN2


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