Cancer Institute, University of Mississippi Medical Center Jackson, MS 39216, USA ; Department of Pathology, University of Mississippi Medical Center Jackson, MS 39216, USA.
Am J Transl Res. 2013 Apr 19;5(3):368-78. Print 2013.
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.
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.
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).
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.
新出现的证据表明，Notch 信号通路可能参与了前列腺癌（PCa）的发展、进展和转移。在本研究中，我们研究了 Jagged-1 和 Notch-1 在人前列腺肿瘤中的表达水平及其与 PCa 进展和转移的关系。
使用组织微阵列（TMA）载玻片上的免疫组织化学（IHC）对 Jagged-1 和 Notch-1 进行检测，该 TMA 载玻片包含 286 例福尔马林固定和石蜡包埋（FFPE）组织标本，具有各种前列腺病变，包括良性变化、高级别前列腺上皮内瘤变（HGPIN）、低级别和高级别 PCa 以及转移性 PCa。
转移性 PCa 和高级别 PCa 中 Jagged-1 的细胞质和膜 IHC 评分明显高于低级别 PCa 和良性前列腺组织。同样，转移性 PCa 和高级别 PCa 中 Notch-1 的细胞质 IHC 评分与低级别 PCa 和良性前列腺组织相比明显升高。Jagged-1 和 Notch-1 在人前列腺组织中的表达之间存在统计学显著相关性。此外，在具有高级别或转移性 PCa（与非裔美国人相比）和具有阳性手术切缘的 PCa 患者（与阴性手术切缘相比）中，Jagged-1 在膜中的高表达更为显著。
我们的结果提供了强有力的证据，表明 Jagged1-Notch1 信号通路的上调在 PCa 的进展和转移中起作用，并表明 Jagged-1 和 Notch-1 可能是区分惰性和侵袭性 PCa 的有用标志物。
