title: E-cadherin protein expression predicts prostate cancer salvage radiotherapy outcomes.
abstract: OBJECTIVE
  Radiotherapy for biochemical prostate cancer recurrence after prostatectomy achieves durable salvage rates of only 40% to 50%. Improved methods of identifying patients unlikely to benefit from salvage radiotherapy are needed. Altered expression of the adhesion molecule E-cadherin may be associated with the invasive and metastatic phenotype. We examined the relationship between E-cadherin expression and outcomes after salvage radiotherapy.
  
  
  METHODS
  E-cadherin expression was examined by immunohistochemistical analysis of a tissue microarray of prostatectomy tissues from patients who underwent salvage radiotherapy. The relation between E-cadherin staining, other risk factors and biochemical failure after salvage radiotherapy was analyzed using Kaplan-Meier and Cox regression methods.
  
  
  RESULTS
  Of 37 analyzable cases 25 showed aberrant E-cadherin expression, while the remainder had normal expression. At a median clinical followup of 40 months univariate analysis demonstrated that E-cadherin staining was not associated with Gleason score, extracapsular extension, surgical margin status, pre-prostatectomy or pre-radiotherapy prostate specific antigen, complete biochemical response after radiotherapy or adjunctive hormonal therapy but it was associated with seminal vesicle invasion. Two-year failure-free survival was 55% in patients with aberrant E-cadherin expression compared with 92% in patients with normal E-cadherin expression (p = 0.02). Multivariate analysis confirmed that aberrant E-cadherin expression was associated with salvage radiotherapy failure (p = 0.03).
  
  
  CONCLUSIONS
  Aberrant E-cadherin staining is associated with increased biochemical failure rates after salvage radiotherapy. Patients with biochemical failure after prostatectomy and aberrant E-cadherin expression are likely to have subclinical disseminated disease. Early systemic therapy may be warranted in these patients.
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109-0010, USA. mray@umich.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ray
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D015820:Cadherins; D017430:Prostate-Specific Antigen