Salivary Adenoid Cystic Carcinoma: Something out of Notching?
Diana Bell, Lucio Miele, Dianna Roberts, Randal Weber, Ehab Hanna. MD Anderson Cancer Center, Houston, TX; UMMC, Jackson, MS
Background: Notch signaling is an important mediator of stem cell biology, tumor formation, angiogenesis and cell fate decision. There are 4 Notch receptors (Notch 1-4) and 5 ligands (Jagged-1 and -2,Delta-like (Dll)-1, -3 and -4). Dysregulation of Notch pathway play a crucial role in breast cancer oncogenesis and it could serve as a target for treatment. Little is known about the Notch pathway in salivary adenoid cystic carcinoma (AdCC). To understand the role of Notch in AdCC, we have undertaken a detailed expression analysis of various Notch receptors and ligands in these tumors.
Design: Archival blocks of 199 AdCC were used for this study, with TMA constructed. Immunohistochemical expression of Notch-1, Notch-2, Notch-4, Jagged-1, Delta were analyzed using mouse monoclonal antibodies. Correlations between Notch receptors/ ligands expression and clinical and histological parameters were assessed by Pearson's Chi-and M-L Chi-square tests. Survival curves were generated using the Kaplan-Meier method and statistical differences by log rank test.
Results: We report a general increase in the expression levels of Notch-1, Notch-2, Notch-4, Jagged-1, Delta proteins in AdCC (Table 1), while weakly/ undetectable levels in normal tissues.
|Marker||AdCC (-)ve||AdCC (+)ve|
|Notch-1||26/175 (15%)||149/175 (85%)|
|Notch-4||24/164 (15%)||149/164 (85%)|
|Notch-2||106/161 (66%)||55/161 (34%)|
|Jagged-1||69/162 (43%)||93/162 (57%)|
|DLL1/Delta||32/161 (20%)||29/161 (80%)|