| AJTR Copyright © 2009-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2013;5(3):368-378
Original Article
Elevated Jagged-1 and Notch-1 expression in high grade and
metastatic prostate cancers
He Zhu, Xinchun Zhou, Samantha Redfield, Jack Lewin, Lucio Miele
Cancer Institute, Department of Pathology, Department of Pharmacology and Toxicology, University of Mississippi
Medical Center, Jackson, MS 39216, USA
Received February 11, 2013; Accepted March 25, 2013; Epub April 19, 2013; Published April 30, 2013
Abstract: Background: Emerging evidence has suggested that Notch signaling pathway may be involved in the
development, progression and metastasis of prostate cancer (PCa). In the present study, we investigated the
expression levels of Jagged-1 and Notch-1 in human prostate tumors and their associations with PCa
progression and metastasis. Methods: Immunohistochemistry (IHC) for Jagged-1 and Notch-1 was performed on
tissue microarray (TMA) slides containing 286 formalin-fixed and paraffin-embedded (FFPE) tissue specimens
with various prostatic pathologies, including benign changes, high grade prostatic intraepithelial neoplasia
(HGPIN), low- and high-grade PCas as well as metastatic PCa. Results: Cytoplasmic and membranous IHC
scores for Jagged-1 in both metastatic PCa and high grade PCa were significantly higher than those in low grade
PCa and in benign prostatic tissues. Similarly, cytoplasmic IHC scores of Notch-1 in both metastatic PCa and
high grade PCa were significantly elevated compared with those observed in low grade PCa and in benign
prostatic tissues. A statistically significant correlation was identified between the expression of Jagged-1 and
Notch-1 in human prostatic tissues. Furthermore, significantly more highly expressed Jagged-1 in membrane
was observed in Caucasian patients with high-grade or metastatic PCa (vs. African Americans) and in PCa
patients with positive surgical margins (vs. negative surgical margins). Conclusion: Our results provide strong
evidence that up-regulation of Jagged1-Notch1 signaling plays a role in PCa progression and metastasis and
suggest that Jagged-1 and Notch-1 may be useful markers in distinguishing indolent and aggressive PCas.
(AJTR1302008).
Keywords: Prostate cancer (PCa), cancer metastasis, Jagged-1, Notch-1, tissue microarray (TMA),
immunohistochemistry (IHC)
Address correspondence to: Dr. Lucio Miele, Cancer Institute, University of Mississippi Medical Center, 2500 N.
State St., Suite G751-5, Jackson, MS 39216, USA. Phone: 601-815-6802/6803; Fax: 601-815-6806; E-mail:
lmiele@umc.edu
Original Article
Elevated Jagged-1 and Notch-1 expression in high grade and
metastatic prostate cancers
He Zhu, Xinchun Zhou, Samantha Redfield, Jack Lewin, Lucio Miele
Cancer Institute, Department of Pathology, Department of Pharmacology and Toxicology, University of Mississippi
Medical Center, Jackson, MS 39216, USA
Received February 11, 2013; Accepted March 25, 2013; Epub April 19, 2013; Published April 30, 2013
Abstract: Background: Emerging evidence has suggested that Notch signaling pathway may be involved in the
development, progression and metastasis of prostate cancer (PCa). In the present study, we investigated the
expression levels of Jagged-1 and Notch-1 in human prostate tumors and their associations with PCa
progression and metastasis. Methods: Immunohistochemistry (IHC) for Jagged-1 and Notch-1 was performed on
tissue microarray (TMA) slides containing 286 formalin-fixed and paraffin-embedded (FFPE) tissue specimens
with various prostatic pathologies, including benign changes, high grade prostatic intraepithelial neoplasia
(HGPIN), low- and high-grade PCas as well as metastatic PCa. Results: Cytoplasmic and membranous IHC
scores for Jagged-1 in both metastatic PCa and high grade PCa were significantly higher than those in low grade
PCa and in benign prostatic tissues. Similarly, cytoplasmic IHC scores of Notch-1 in both metastatic PCa and
high grade PCa were significantly elevated compared with those observed in low grade PCa and in benign
prostatic tissues. A statistically significant correlation was identified between the expression of Jagged-1 and
Notch-1 in human prostatic tissues. Furthermore, significantly more highly expressed Jagged-1 in membrane
was observed in Caucasian patients with high-grade or metastatic PCa (vs. African Americans) and in PCa
patients with positive surgical margins (vs. negative surgical margins). Conclusion: Our results provide strong
evidence that up-regulation of Jagged1-Notch1 signaling plays a role in PCa progression and metastasis and
suggest that Jagged-1 and Notch-1 may be useful markers in distinguishing indolent and aggressive PCas.
(AJTR1302008).
Keywords: Prostate cancer (PCa), cancer metastasis, Jagged-1, Notch-1, tissue microarray (TMA),
immunohistochemistry (IHC)
Address correspondence to: Dr. Lucio Miele, Cancer Institute, University of Mississippi Medical Center, 2500 N.
State St., Suite G751-5, Jackson, MS 39216, USA. Phone: 601-815-6802/6803; Fax: 601-815-6806; E-mail:
lmiele@umc.edu
 | |  | |  | |  | |  | |  | |  |