Abstract
Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102). EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center. Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified.
Highlights
Prostate cancer (PC) is the second most common cause of cancer related death in men, with approximately 913,000 new cases world wide in 2008 [1]
The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for digital rectal examination (DRE)
This study evaluates a transcription factor secreted by prostate cancer as a simple ELISA test without the requirement for digital rectal examination
Summary
Prostate cancer (PC) is the second most common cause of cancer related death in men, with approximately 913,000 new cases world wide in 2008 [1]. Organ-confined PC can be cured in a large proportion of patients by surgery or radiotherapy. Advanced and metastatic PC continues to be associated with a poor prognosis [2]. Serum prostate specific antigen (PSA) has been used as a cancer marker for initial diagnosis, monitoring of response to treatment, prediction of PC risk and of treatment outcome. As a prostate specific and not prostate cancer-specific marker, it lacks both sensitivity and spe-. Authors' Affiliations: 1Postgraduate Medical School, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom; 2St. George's, University of London, London, United Kingdom; 3Royal Surrey County Hospital, Guildford, United Kingdom; 4Uro-Oncology Research Group, CRUK Cambridge Research Institute, Cambridge, UK; 5Basingstoke Hospital, Basingstoke, United Kingdom
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