Abstract
Background Notch signaling evolves as an important mediator of stem cell biology, tumor formation, angiogenesis and cell fate decision. In mammals, there are four Notch receptors (Notch 1–4) and five ligands (Jagged-1 and -2, Delta-like (Dll)-1, -3 and -4). Dysregulation of Notch pathway has been found to play a crucial role in breast cancer oncogenesis and it could serve as a target for treatment. Relatively little is known about the pattern of expression of various components of Notch pathway in salivary adenoid cystic carcinoma (AdCC). To understand the role of Notch pathway in AdCC, we have undertaken a detailed expression analysis of various Notch receptors and their ligands in these tumors. Design Archival paraffin blocks of 199 AdCC were used and TMA were constructed. Immunohistochemical expression of Notch-1, Notch-2, Notch-4, Jagged-1, Delta were analyzed. Correlations between Notch receptors/ligands expression and clinical and histological parameters were assessed by Pearson’s Chi-square and M-L Chi-square tests; survival curves were generated with Kaplan–Meier method, statistical differences by log rank test. Results We found a general increase in the expression levels of Notch-1, Notch-2, Notch-4, Jagged-1, Delta proteins in AdCC, while weakly/undetectable levels in normal tissues. AdCC expressed the biomarkers as follow: 85% for Notch-1 (149/175) and Notch-4 (149/164), 80% for DLL1/Delta, 57% for Jagged 1 and 34% for Notch-2 (55/161). No significant statistical correlation was found between individual markers and clinico-pathological parameters. The combination of Jagged 1 and Notch 2 showed a significant p value (p 0.03644) for vital status at last contact within 12 years of presentation. Conclusions High expression of Notch receptors and ligands in AdCC places Notch signaling as a key player in AdCC pathogenesis. Our data provides the direct evidence for a relationship between Jagged-1/Notch-2 co-expression and better overall patient survival in AdCC. Targeting the Notch signaling pathway could provide therapeutic benefits.
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