Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
Histopathology. 2012 Apr;60(5):826-37. doi: 10.1111/j.1365-2559.2011.04158.x. Epub 2012 Feb 20.
The aim of this study was to investigate the significance of the expression of Notch-related molecules in endometrial carcinoma.
The expression of Notch receptors (Notch1 and 3) and Notch ligands [Jagged (JAG) 1 and Delta-like (DLL) 4] was examined immunohistochemically in 37 normal and 76 malignant endometrial tissue samples. For each section, immunohistochemical staining was scored using a positivity index (PI, full score; 200). The effects of a Notch inhibitor, DAPT, on cell proliferation, invasion and motility were investigated using endometrial carcinoma cell lines. The PIs for Notch1 (mean±SD 90.4±15.3), Notch3 (95.6 ± 20.4), JAG1 (95.5±10.0) and DLL4 (88.2±9.6), were significantly higher in endometrial carcinoma than normal endometrium. The PI for Notch1 was associated significantly with advanced International Federation of Gynecologists & Obstetricians (FIGO) stage. In addition, patients with tumours showing high expression of both Notch1 and JAG1 had a poor prognosis compared with those having double-negative carcinomas (P=0.015). DAPT suppressed invasiveness of cells derived from the endometrial carcinoma cell line KLE.
The Notch1-JAG1 axis may enhance the invasive properties of endometrial carcinomas, which suggests the Notch pathway may be a promising target for the treatment of this malignancy.
本研究旨在探讨 Notch 相关分子在子宫内膜癌中的表达意义。
采用免疫组织化学方法检测了 37 例正常和 76 例恶性子宫内膜组织中 Notch 受体（Notch1 和 Notch3）和 Notch 配体[Jagged（JAG）1 和 Delta-like（DLL）4]的表达。对每个切片，使用阳性指数（PI，满分为 200）进行免疫组化染色评分。使用子宫内膜癌细胞系研究 Notch 抑制剂 DAPT 对细胞增殖、侵袭和迁移的影响。Notch1（平均±SD 90.4±15.3）、Notch3（95.6 ± 20.4）、JAG1（95.5±10.0）和 DLL4（88.2±9.6）的 PI 在子宫内膜癌中明显高于正常子宫内膜。Notch1 的 PI 与国际妇产科联合会（FIGO）晚期分期显著相关。此外，与双阴性癌相比，Notch1 和 JAG1 高表达的肿瘤患者预后较差（P=0.015）。DAPT 抑制了来源于子宫内膜癌细胞系 KLE 的细胞的侵袭性。
Notch1-JAG1 轴可能增强子宫内膜癌的侵袭特性，提示 Notch 通路可能是治疗这种恶性肿瘤的有前途的靶点。
