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

dc.contributor.author

Armstrong, AJ

dc.contributor.author

Healy, P

dc.contributor.author

Halabi, S

dc.contributor.author

Vollmer, R

dc.contributor.author

Lark, A

dc.contributor.author

Kemeny, G

dc.contributor.author

Ware, K

dc.contributor.author

Freedland, SJ

dc.coverage.spatial

England

dc.date.accessioned

2015-11-20T21:03:05Z

dc.date.issued

2016-03

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.identifier

http://www.ncbi.nlm.nih.gov/pubmed/26458958

dc.identifier

pcan201546

dc.identifier.eissn

1476-5608

dc.identifier.uri

https://hdl.handle.net/10161/10917

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

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

duke.contributor.orcid

Armstrong, AJ|0000-0001-7012-1754

duke.contributor.orcid

Halabi, S|0000-0003-4135-2777

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
EP TMA PCAN 2015.pdf
Size:
1.39 MB
Format:
Adobe Portable Document Format