title: Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer.
abstract: What's known on the subject? and What does the study add? There are a lot of potential prostate cancer biomarkers being evaluated. All aim to improve on the sensitivity and specificity of PSA. EN2 was recently shown by our group to have better sensitivity and specificity than PSA. EN2 is a simple ELISA test and is not dependent on other parameters, even PSA, unlike all the other current biomarkers under evaluation. To date, no marker correlates with the amount of cancer present - the present study shows this positive correlation with EN2 in men undergoing prostatectomy. The potential utility of this work is that by knowing that the level of EN2 corresponds to the amount of cancer present, irrelevant of tumour grade and number of cancer foci, we can define an EN2 level corresponding to small cancers, which can then undergo surveillance. We are conducting a further study that is aimed at determining whether the levels of EN2 in urine can indicate 'significant' vs 'non-significant cancer' using the threshold of 0.5 mL cancer (after Epstein's work).
  
  
  OBJECTIVE
  To evaluate the relationship between levels of a recently described prostate cancer biomarker engrailed-2 (EN2) in urine and cancer volume in men who had undergone radical prostatectomy (RP) for prostate cancer. To date, prostate-specific antigen (PSA) levels have not reliably predicted prostate cancer volume. Reliable volume indicator biomarker(s) may aid management decisions, e.g. active treatment vs active surveillance.
  
  
  METHODS
  Archived patient samples from the Aarhus Prostate Cancer Project, Denmark, were assessed. Pre-treatment mid-stream urines, without preceding prostatic massage, were collected and stored at -80 °C. Urinary EN2 levels were measured by a recently published enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In all, 88 of the whole cohort of 125 men (70%) were positive for EN2 in their urine (>42.5 µg/L); 38/58 (65%) men where cancer volume data was available. There was no statistical relationship between urinary EN2 levels and serum PSA levels. PSA levels did not correlate with tumour stage, combined Gleason grade, total prostatic weight or cancer volume. There was a strong statistical relationship between urinary EN2 and prostate cancer volume by linear regression (P = 0.006). Higher EN2 levels correlated with tumour stage T1 vs T2 (P = 0.027).
  
  
  CONCLUSIONS
  Pre-surgical urinary EN2 levels were associated with increasing tumour stage and closely reflected the volume of cancer in RP specimens. Given the ease of collection (no prostatic massage required) and the simplicity, low cost and robustness of the assay, EN2 may become a useful biomarker in not only identifying which patients have prostate cancer but may also facilitate risk stratification by indicating the burden of tumour volume.
authors.affiliation: Oncology, Postgraduate Medical School, Guildford, UK. h.pandha@surrey.ac.uk
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
authors.forename: Karen D
authors.initials: KD
authors.lastname: Sorensen
authors.forename: Thorsten F
authors.initials: TF
authors.lastname: Orntoft
authors.forename: Stephen
authors.initials: S
authors.lastname: Langley
authors.forename: Soren
authors.initials: S
authors.lastname: Hoyer
authors.forename: Michael
authors.initials: M
authors.lastname: Borre
authors.forename: Richard
authors.initials: R
authors.lastname: Morgan
mesh_terms: D000368:Aged; D018398:Homeodomain Proteins / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000652:urine*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery / Q000652:urine*; D047368:Tumor Burden; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000099266:Engrailed 2 Protein