Abstract 410: Elevated Jagged-1 and Notch-1 expression in high grade and metastatic prostate cancers.

Abstract

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 prostate cancer 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 tissue specimens with various prostatic disorders, including benign changes, high grade prostatic intraepithelial neoplasia (HGPIN), low and high grade prostate cancers as well as metastatic prostate cancers. The expression levels of Jagged-1 and Notch-1 were reported as a final IHC score calculated as staining extent score (0-3) multiplied by intensity score (0-3); with a maximal score equal to 9. ANOVA and t-test were employed to analyze the difference of IHC scores among and between different pathologic categories Results: Jagged-1 cytoplasmic IHC scores in both metastatic PCa (5.92 ± 2.12, Mean ± SD) and high grade PCa (5.74 ± 2.45) were significantly higher than those in low grade PCa (3.55 ± 2.02, p = 9.02E-07 and 4.65E-08, respectively), in HGPIN (4.50 ± 2.34, p = 0.023 and 0.030, respectively), and in prostatic tissues with benign changes (3.39 ± 1.85, p = 7.96E-07 and 2.47E-07, respectively). In addition, Jagged-1 membranous IHC scores in both metastatic PCa (3.05 ± 3.52) and high grade PCa (2.41 ± 2.90) were also significantly higher than those in low grade PCa (0.71 ± 1.42, p = 1.48E-05 and 3.40E-06, respectively) and in prostatic tissues with benign changes (0.82 ± 1.28, p = 3.19E-04 and 0.001, respectively). Similarly, Notch-1 cytoplasmic IHC scores in both metastatic PCa (2.22 ± 2.11) and high grade PCa (1.10 ± 1.68) were significantly elevated when compared with the IHC scores observed in low grade PCa (0.51 ± 1.15, p = 3.63E-06 and 0.023, respectively) and in prostate tissues with benign changes (0.48 ± 1.01, p = 3.37E-06 and 0.017, respectively). Furthermore, significantly more highly expressed Jagged-1 in membrane was observed in Caucasians (vs. African Americans) and in positive surgical resection margin group (vs. negative surgical resection margin group). Conclusions: Our results provide strong evidence that dysregulation of Jagged 1-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 prostate cancers. Citation Format: He Zhu, Xinchun Zhou, Samantha Redfield, Jack Lewin, Lucio Miele. Elevated Jagged-1 and Notch-1 expression in high grade and metastatic prostate cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 410. doi:10.1158/1538-7445.AM2013-410