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

Armstrong, AJ

Healy, P

Halabi, S

Vollmer, R

Lark, A

Kemeny, G

Ware, K

Freedland, SJ

England

2015-11-20T21:03:05Z

2016-03

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.

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

pcan201546

1476-5608

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

eng

Springer Science and Business Media LLC

Prostate Cancer Prostatic Dis

10.1038/pcan.2015.46

Aged

Biomarkers, Tumor

Cadherins

Cell Plasticity

Disease-Free Survival

Epithelial Cells

Homeodomain Proteins

Humans

Ki-67 Antigen

Male

Middle Aged

Neoplasm Recurrence, Local

Nuclear Proteins

Prostate-Specific Antigen

Prostatic Neoplasms

Snail Family Transcription Factors

Tissue Array Analysis

Transcription Factors

Twist-Related Protein 1

Vimentin

Zinc Finger E-box-Binding Homeobox 1

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

Journal article

Armstrong, AJ|0000-0001-7012-1754

Halabi, S|0000-0003-4135-2777

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

40

45

1

Basic Science Departments

Biostatistics & Bioinformatics

Clinical Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Medicine

Medicine, Medical Oncology

Pathology

Pharmacology & Cancer Biology

School of Medicine

Surgery

Surgery, Vascular Surgery

Published

19