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

Loading...
Thumbnail Image

Date

2016-03

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

203
views
297
downloads

Citation Stats

Attention Stats

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1038/pcan.2015.46

Publication Info

Armstrong, AJ, P Healy, S Halabi, R Vollmer, A Lark, G Kemeny, K Ware, SJ Freedland, et al. (2016). Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer. Prostate Cancer Prostatic Dis, 19(1). pp. 40–45. 10.1038/pcan.2015.46 Retrieved from https://hdl.handle.net/10161/10917.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Armstrong

Andrew John Armstrong

Professor of Medicine

I am a clinical and translational investigator focused on precision therapies and biomarkers in advanced prostate and other GU cancers.  I oversee a large research team of clinical and lab based investigators focused on improving patient outcomes, preventing metastatic disease, and understanding the biology of aggressive prostate cancer.  Some key themes:
1. Predictors of sensitivity and clinical efficacy of therapies in advanced prostate cancer
2. Novel designs of clinical trials and pharmacodynamic/translational studies in prostate, kidney, bladder cancer
3. Pre-operative models for drug development of novel agents in human testing in prostate cancer
4. Novel therapies and drug development for prostate, renal, bladder, and testicular cancer
5. Design of rational combination therapies in men with metastatic hormone-refractory prostate cancer
6. Developing prognostic and predictive models for progression and survival in metastatic prostate cancer
7. Examining surrogate markers of mortality in metastatic prostate cancer
8. Clear cell and non-clear cell renal cell carcinoma: natural history, sensitivity to novel agents including mTOR and VEGF inhibition

Halabi

Susan Halabi

James B. Duke Distinguished Professor

Design and analysis of clinical trials, statistical analysis of biomarker and high dimensional data, development and validation of prognostic and predictive models.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.