Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.
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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.
Neoplasm Recurrence, Local
Snail Family Transcription Factors
Tissue Array Analysis
Twist-Related Protein 1
Zinc Finger E-box-Binding Homeobox 1
Published Version (Please cite this version)10.1038/pcan.2015.46
Publication InfoArmstrong, AJ; Healy, P; Halabi, S; Vollmer, R; Lark, A; Kemeny, G; ... Freedland, SJ (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.
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Professor of Medicine
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-refra
Professor of Biostatistics and Bioinformatics
Design and analysis of clinical trials, statistical analysis of biomarker and high dimensional data, development and validation of prognostic and predictive models.
Associate Professor of Pathology
My research interests have to do with practical problems in the interface between the practice of pathology and clinical outcomes of patients, including their diagnosis, prognosis, and events of failure. Often I use mathematical or statistical approaches to deal with these issues.
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