Expression of Netrin-1 and DCC in Adenoid Cystic Carcinoma

Objectives: Netrin-1 and its receptors DCC are critical for neuronal migration in nervous system development. Recent studies have shown that they are widely expressed outside the nervous system and they may play important roles in cancers. However, expression of Netrin-1 and DCC in adenoid cystic carcinoma (ACC) has been poorly documented. The present study was designed to evaluated the expression of these cytokines in relation to clinicopathological outcome in ACC.

Methods: The expression of Netrin-1 and DCC in 20 surgically resected ACCs and in tow cancer cell lines was examined by immunohistochemical staining and RT-PCR. We also invested the relationship between Netrin-1 and clinicopathologic features of all cases.

Results: Homogeneous cytoplasmic Netrin-1 protein expression could be observed in the endothelial cells and tumor cells of most tumors. Netrin-1 staining activities in ACCs were more significant than those in normal gland tissues (P < 0.05). However, DCC expression was only appeared in endothelial cells and the tumor cells tended to silence DCC expression. In addition, all of the ACC cell lines lost normal DCC expression and no change were observed in the presence of netrin-1. In three histologic types of ACCs, the Netrin-1 expression was significantly higher in solid type than in cribriform and tubular types (P < 0.05). The Netrin-1 expression was significantly correlated with clinical stage, tumor size and perineural invasion.

Conclusion: Our observations suggest that Netrin-1/DCC signaling may contribute to the tumorigenesis of adenoid cystic carcinoma.