[1268] 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.

Markers expression in AdCC
MarkerAdCC (-)veAdCC (+)ve
Notch-126/175 (15%)149/175 (85%)
Notch-424/164 (15%)149/164 (85%)
Notch-2106/161 (66%)55/161 (34%)
Jagged-169/162 (43%)93/162 (57%)
DLL1/Delta32/161 (20%)29/161 (80%)


Subcellular localization for Notch-1, Notch-2 and Notch-4 was predominantly nuclear and cytoplasmic, while cytoplasmic/ membranous for Jagged-1 and Delta-1 ligands. No significant statistical correlation were found between individual markers and clinico-pathological parameters. The combination of Jagged 1 and Notch 2 showed a p value of 0.036 for vital status at last contact within 12 years of presentation; the worst survival was associated with having one of the markers and the best survival was in the group that had both of them. This may be explained that in a setting that has a ligand (Jagged-1) and Notch-2 together, there is a tumor suppressive effect. On the other hand, Jagged-1 (and Notch- 2) alone may possess tumor-promoting functions and would account for a poor prognostic significance.
Conclusions: High expression of Notch receptors and ligands in AdCC, places Notch signaling as a key player in AdCC pathogenesis. Our data provides the first direct evidence for a relationship between Jagged-1/Notch-2 co-expression and better overall patient survival in human salivary adenoid cystic carcinoma. Targeting the Notch signaling pathway could provide therapeutic benefits.
Category: Head & Neck

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 151, Tuesday Morning

 

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