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Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.

dc.contributor.author Armstrong, AJ
dc.contributor.author Freedland, SJ
dc.contributor.author Halabi, Susan
dc.contributor.author Healy, Patrick
dc.contributor.author Kemeny, G
dc.contributor.author Lark, A
dc.contributor.author Vollmer, Robin T
dc.contributor.author Ware, Kathryn E
dc.coverage.spatial England
dc.date.accessioned 2015-11-20T21:03:05Z
dc.date.issued 2016-03
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26458958
dc.identifier pcan201546
dc.identifier.uri http://hdl.handle.net/10161/10917
dc.description.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.
dc.language eng
dc.relation.ispartof Prostate Cancer Prostatic Dis
dc.relation.isversionof 10.1038/pcan.2015.46
dc.subject Aged
dc.subject Biomarkers, Tumor
dc.subject Cadherins
dc.subject Cell Plasticity
dc.subject Disease-Free Survival
dc.subject Epithelial Cells
dc.subject Homeodomain Proteins
dc.subject Humans
dc.subject Ki-67 Antigen
dc.subject Male
dc.subject Middle Aged
dc.subject Neoplasm Recurrence, Local
dc.subject Nuclear Proteins
dc.subject Prostate-Specific Antigen
dc.subject Prostatic Neoplasms
dc.subject Snail Family Transcription Factors
dc.subject Tissue Array Analysis
dc.subject Transcription Factors
dc.subject Twist-Related Protein 1
dc.subject Vimentin
dc.subject Zinc Finger E-box-Binding Homeobox 1
dc.title Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26458958
pubs.begin-page 40
pubs.end-page 45
pubs.issue 1
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Pathology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Vascular Surgery
pubs.publication-status Published
pubs.volume 19
dc.identifier.eissn 1476-5608


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