Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells

Aims: The aim of this study was to investigate the significance of the expression of Notch-related molecules in endometrial carcinoma. Methods and results: 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. Conclusions: 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.