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

Abstract 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-muscl...

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Bibliographic Details
Published in:European journal of cancer (1990) 2013-06, Vol.49 (9), p.2214-2222
Main Authors: Morgan, Richard, Bryan, Richard T, Javed, Saqib, Launchbury, Francesca, Zeegers, Maurice P, Cheng, K.K, James, Nicholas D, Wallace, D. Michael A, Hurst, Carolyn D, Ward, Douglas G, Knowles, Margaret A, Pandha, Hardev
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Biomarker
Biomarkers, Tumor - urine
Bladder cancer
Cell Line, Tumor
Diagnostic
EN2
Hematology, Oncology and Palliative Medicine
Homeodomain Proteins - urine
Humans
Medical sciences
Middle Aged
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Nerve Tissue Proteins - urine
Pharmacology. Drug treatments
Prospective Studies
Sensitivity and Specificity
Tumors
Urinary Bladder Neoplasms - diagnosis
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Summary:Abstract 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.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2013.01.019