Abstract 3638: Detecting prostate cancer in BRCA1 and BRCA2 mutation carriers: A role for EN2
Authors: Killick Emma , Morgan Richard , Launchbury Francesca , Annels Nicola , Bancroft Elizabeth , Page Elizabeth , Castro Elena , Kote-Jarai Zsofia ,   The IMPACT steering committee and IMPACT collaborators, Eeles Rosalind , Pandha Hardev 
Published: August 2012

Abstract
EN2 is part of the HOX gene family and plays a role in foetal development. More recently a potential oncogenic role for the protein has been postulated and its utility as a cancer biomarker has been explored in prostate cancer (PrCa) and breast cancer. Carriers of mutations in the BRCA1 and BRCA2 genes have an increased risk of PrCa (1.8-fold and 5-fold respectively) and their tumours tend to be more aggressive and advanced than sporadic cases. Currently there is no national screening program for BRCA mutation carriers in the UK, and the IMPACT study was set up to evaluate PSA screening in this particular group. Here we analyse the efficacy of the urinary EN2 protein and auto-antibody against EN2 in serum and urine as markers of early cancer detection within this higher risk group. Urine and serum were taken from the IMPACT screening study which enrolled individuals aged between 40 and 69 who were unaffected by PrCa at time of enrolment into the study (n= 418). All participants were from families harbouring a BRCA1 or BRCA2 mutation and were either BRCA mutation carriers themselves or controls with a negative predictive BRCA genetic test. They underwent annual PSA test with a PSA of &gt; 3.0 ng/ml triggering a diagnostic biopsy. Annual urine and serum samples were collected from this cohort. EN2 protein was measured in the urine using an ELISA; (positive = &gt; 42.5ng/ml). The autoantibody was measured in serum and urine; (positive = measurement of 2 standard deviations above the mean value when measured in a cohort of healthy volunteers). Using detection of EN2 protein in urine alone our initial results demonstrated the test had a sensitivity of 71.4% and a specificity of 75.4% when discriminating between those with a positive biopsy and those with a negative biopsy; the ROC AUC was 0.767. The difference in EN2 level between those diagnosed with cancer and those who were not was significant (p = &lt;0.001). EN2 antibody measured in serum was less sensitive but more specific that the urinary protein (33.3% and 83.6% respectively), when combined with urinary protein the sensitivity is 85.7% with a specificity of 63.3% and ROC AUC 0.745. Further samples are in the process of being analysed and data and results of these will be presented. In addition a new assay to measure urinary antibody is currently under development and results from this test will be also shown. EN2 protein and auto-antibody measurement warrants further investigation as a PrCa biomarker in this higher risk group with genetic predisposition to PrCa.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3638. doi:1538-7445.AM2012-3638