title: Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Postgraduate Medical School, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom. r.morgan@surrey.ac.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Morgan
authors.forename: Angela
authors.initials: A
authors.lastname: Boxall
authors.forename: Aagna
authors.initials: A
authors.lastname: Bhatt
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Richard
authors.initials: R
authors.lastname: Hindley
authors.forename: Stephen
authors.initials: S
authors.lastname: Langley
authors.forename: Hayley C
authors.initials: HC
authors.lastname: Whitaker
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ismail
authors.forename: Hamish
authors.initials: H
authors.lastname: Whitaker
authors.forename: Nicola
authors.initials: N
authors.lastname: Annels
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Michael
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D015153:Blotting, Western; D045744:Cell Line, Tumor; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D018398:Homeodomain Proteins / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000652:urine*; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D012680:Sensitivity and Specificity; D000099266:Engrailed 2 Protein
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D017430:Prostate-Specific Antigen; D000099266:Engrailed 2 Protein