title: Multi-transcript profiling in archival diagnostic prostate cancer needle biopsies to evaluate biomarkers in non-surgically treated men.
abstract: BACKGROUND
  Most biomarkers in prostate cancer have only been evaluated in surgical cohorts. The value of these biomarkers in a different therapy context remains unclear. Our objective was to test a panel of surgical biomarkers for prognostic value in men treated by external beam radiotherapy (EBRT) and primary androgen deprivation therapy (PADT).
  
  
  METHODS
  The Fluidigm® PCR array was used for multi-transcript profiling of laser microdissected tumours from archival formalin-fixed diagnostic biopsies of patients treated by EBRT or PADT. Cases were matched for disease characteristics and had known 5 year biochemical relapse outcomes (n = 60). Results were validated by immunohistochemistry in a custom needle biopsy tissue microarray. Six biomarkers previously tested only in surgical cohorts were analysed (PTEN, E-Cadherin, EGFR, EZH2, PSMA, MSMB). Transcript and protein expression was correlated with clinical outcome analysed using Kruskal Wallis, Fisher's test and Cox proportional hazard model.
  
  
  RESULTS
  Altered expression of E-Cadherin (p = 0.008) was associated with early relapse after EBRT. In PADT treated men however only altered MSMB transcript was prognostic for early relapse (p = 0.001). The remaining biomarkers however did not demonstrate prognostic ability in either cohort. In a separate tissue array we validated altered E-Cadherin protein as a predictor of early relapse after EBRT (n = 47) (HR 0.34, CI p = 0.02) but not in PADT treated men (n = 63).
  
  
  CONCLUSIONS
  We demonstrate proof of principle of multiple transcript profiling in archival diagnostic biopsies of non-surgically treated men for biomarker discovery. We identify a role for E-Cadherin as a novel biomarker of early relapse following EBRT.
authors.forename: Naveen
authors.initials: N
authors.lastname: Kachroo
authors.forename: Anne Y
authors.initials: AY
authors.lastname: Warren
authors.affiliation: Translational Prostate Cancer Group, Hutchison/MRC research centre, University of Cambridge, Hills Road, CB1 0XZ Cambridge, UK. vjg29@cam.ac.uk.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Gnanapragasam
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D015415:Biomarkers; D001707:Biopsy, Needle; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D061766:Proton Therapy; D012008:Recurrence; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers