AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2011;3(1):90-99

Original Article
Molecular signature of Epithelial-Mesenchymal Transition (EMT) in
human prostate cancer bone metastasis

Seema Sethi, Jill Macoska, Wei Chen, Fazlul H. Sarkar

Departments of Pathology & Biostatistics, Karmanos Cancer Institute, Wayne State University School of Medicine,
Detroit, MI and Department of Urology and Comprehensive Cancer Center, University of Michigan Medical School,
Ann Arbor, MI, USA.

Received October 15, 2010; Accepted October 21, 2010; Epub October 23, 2010; Published January 1, 2011

Abstract: Prostate cancer (PCa) has a predilection to metastasize to bone. Before metastasis can occur there is
transition of the sessile epithelial cancer cells to become motile and invasive mesenchymal phenotypes by an
important albeit transient process called Epithelial-to-Mesenchymal Transition (EMT). The cascade of molecular
events triggered by this process is clinically relevant as they are associated with cancer stem-like cells (CSC),
decreased senescence and eventual drug resistance phenotype. We interrogated some EMT marker that have
been implicated in primary and bone metastasis of PCa using archived patient samples.  Using an
immunohistochemical approach, E-cadherin, Vimentin, ZEB1, Notch-1, PDGF-D and NF-B were analyzed.
Cases were microscopically scored using intensity (0, +1, +2, +3) and percentage of positive cells. Data was
statistically analyzed using Fischer’s Exact Test. Aberrant expression of EMT markers E-cadherin, Vimentin,
PDGF-D, NF-κB, Notch-1 and ZEB1 was observed in PCa (primary tumor specimen) and bone metastasis
tissues. The aberrant expression pattern varied according to the location within the tumor with higher expression
was observed more at the invasive tumor front (ITF) vs. the center of the tumor. Notch-1 was significantly over-
expressed in bone metastasis compared to primary PCa (p=0.057). The expression levels, intensity and % of
positive cells of the remaining markers were not statistically significant in PCa vs. bone metastasis.  In
conclusion, protein expression analysis revealed the existence of EMT phenotype in the PCa and bone
metastasis. Variation in the aberrant expression patterns at the invasive tumor front indicates the role of EMT
markers in tumor invasion. Our results suggest that Notch-1 could play a in PCa bone metastasis. Studies in
larger patient cohorts are warranted before these EMT molecular markers can be translated to the clinical use.

Key words: Endocrine surgery, research funding, surgeon-scientist, surgical research, endocrine surgery
research, education

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Address all correspondence to:
Fazlul H. Sarkar, PhD
Department of Pathology, Barbara Ann Karmanos Cancer Institute,
Wayne State University School of Medicine,
740 Hudson Webber Cancer Research Center,
4100 John R Street
Detroit, MI 48201
Tel: 313-576-8327; Fax: 313-576-8389;
Email: fsarkar@med.wayne.edu