Elevated Jagged-1 and Notch-1 expression in high grade and metastatic prostate cancers

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.

Keywords: Jagged-1; Notch-1; Prostate cancer (PCa); cancer metastasis; immunohistochemistry (IHC); tissue microarray (TMA).

Figure 1

Representative examples of Jagged-1 (upper panel) and Notch-1 (lower panel) expression levels observed in prostatic tissue with benign changes (A); HGPIN (B); low grade PCa (C); high grade PCa (D) and metastatic PCa (E).

Figure 2

Comparison of Jagged-1 IHC scores between positive and negative surgical margin groups. Of 85 prostate cancer patients who were performed with radical prostatectomy, 27 had positive surgical margin and 58 had negative surgical margin. Columns, mean of IHC scores; bars, ± SD..

Figure 3

Comparison of Jagged-1 IHC scores between positive and negative capsular invasion (CI) groups. Of 85 prostate cancer patients who were performed with radical prostatectomy, 24 had positive capsular invasion and 61 had negative capsular invasion. Columns, mean of IHC scores; bars, ± SD.