The Expression Levels of Cytoplasmic and Membranous Jagged-1 Are Associated with Progression and Metastasis of Prostate Cancer
Xinchun Zhou, He Zhu, Samantha Redfield, Mehri Mollaee, Zhi He, Jack Lewin, Lucio Miele. University of Misissippi Medical Center, Jackson, MS; University of Mississippi Medical Center, Jackson, MS
Background: A few previous studies have suggested that Jagged-1, one of ligands for Notch receptors and an important component of Notch signaling pathways, is associated with bone metastasis of prostate cancer. In this study, we investigated the subcellular location of Jagged-1 and the association of its expression levels with various prostatic pathologies.
Design: Immunohistochemistry (IHC) for Jagged-1 was performed on tissue microarray (TMA) slides containing 238 formalin-fixed and paraffin-embedded tissues from various organs/tissues, including 42 benign changes, 24 prostatic intraepithelial neoplasia (PIN), 146 localized prostate cancers and 31 metastatic prostate cancers. The expression level of Jagged-1 was reported as a final IHC score calculated as staining extent score (0-3) multiplied by intensity score (0-3) with a maximal score of 9. ANOVA and t-test were employed to analyze the difference of IHC scores among and between different pathologic categories.
Results: IHC signals for Jagged-1 were seen in both cytoplasm (in 243 specimens) and cellular membranes (in 108 specimens). The expression levels of both cytoplasmic and membranous Jagged-1 were the highest in metastatic prostate cancer. These were significantly higher than that in localized prostate cancer or in benign prostatic changes. Similarly, IHC scores for both membranous and cytoplasmic Jagged-1were significantly higher in localized prostate cancer as compared with benign changes. We also found that high grade localized prostate cancers had significantly higher membranous and cytoplasmic IHC scores than low grade localized prostate cancers. Although the overall expressed level of Jagged-1were higher in cytoplasm than that in plasma membrane, additional significant differences in Jagged-1 IHC scores were only observed in membrane: significantly higher in Caucasians (vs. African Americans) and in positive capsule invasion (vs. negative capsule invasion).
Conclusions: This study indicates that expression levels of both membranous and cytoplasmic Jagged-1correlate with progression and metastasis of prostate cancer. The expression level of membranous Jagged-1 may more precisely predict the progression and metastasis of prostate cancer as compared with cytoplasmic Jagged-1.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 147, Wednesday Afternoon