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Expression of engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker
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Morgan, Richard, Bryan, Richard T., Javed, Saqib, Launchberry, Francesca, Zeegers, Maurice, Cheng, Kar K. , James, Nicholas D., Wallace, Michael A., Hurst, Carolyn D., Ward, Douglas G., Knowles, Margaret A. and Pandha, Hardev (2013) Expression of engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker. European Journal of Cancer, 49 (9). pp. 2214-2222. doi:10.1016/j.ejca.2013.01.019 ISSN 0959-8049.
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Official URL: http://dx.doi.org/10.1016/j.ejca.2013.01.019
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.
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