title: Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.
abstract: BACKGROUND
  Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery.
  
  
  METHODS
  Men with localized PC treated with radical prostatectomy at the Durham VA Medical Center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1 and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics an risk of PSA recurrence over time.
  
  
  RESULTS
  Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; three died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N-cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence or Gleason sum were noted for SNAIL, ZEB1, vimentin or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (P=0.043), National Comprehensive Cancer Network risk (P=0.013) and PSA recurrence (hazard ratio 1.07, P=0.016).
  
  
  CONCLUSIONS
  The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.
authors.affiliation: Department of Medicine/Division of Medical Oncology, Durham, NC, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Durham, NC, USA.
authors.forename: P
authors.initials: P
authors.lastname: Healy
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Halabi
authors.affiliation: Department of Pathology, Duke University and the Durham VA Medical Center, Durham, NC, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vollmer
authors.affiliation: Department of Pathology, Duke University and the Durham VA Medical Center, Durham, NC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lark
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Durham, NC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kemeny
authors.affiliation: Department of Molecular Genetics and Microbiology, Durham, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ware
authors.affiliation: Department of Surgery/Division of Urology, Duke University and the Durham VA Medical Center, now at Cedars-Sinai Medical Center, Durham, NC, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D000066670:Cell Plasticity / Q000235:genetics; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000071250:Snail Family Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D017430:Prostate-Specific Antigen