DRD2/DARPP-32 expression correlates with lymph node metastasis and tumor progression in patients with esophageal squamous cell carcinoma.

Abstract

Dopamine receptors (DRs) are members of seven transmembrane domain trimeric guanosine 5'-triphosphate (GTP)-binding protein-coupled receptor family. Through dopamine receptor activation, dopamine plays a significant role in regulating gene expression, such as induced tumor cell migration. We investigated DRD1 and DRD2 expressions in patients with esophageal squamous cell carcinoma (ESCC) for immunohistochemistry and analyzed differences between DRD1, DRD2, and DARPP-32 expressions of clinicopathological features in 122 patients with ESCC. DRD1 immunostaining correlated with the pathologic grade (P = 0.0127), and DRD2 immunostaining correlated with the pathologic stage (P = 0.0432) and pN classification (P = 0.0112). A significant correlation was found between DRD1 and DRD2 expression (P = 0.0292). However, no correlation was observed between DRD1/DRD2 expression and DARPP-32 expression (P = 0.4555 and 0.4774, respectively). No correlation was observed between the DRD1/DRD2 expression and patient prognosis. To find the cooperative role between DRD1, DRD2, and DARPP-32 expressions, patients were classified into the different groups. In the DRD2/DARPP-32 combination, the (+/-) group was significantly correlated with pathologic stage (P = 0.0006), lymph node metastasis (P = 0.0001), pT (P = 0.0287), and tumor size (P = 0.0202). Moreover, patients with this combination showed a lower survival rate compared with the other three groups (P = 0.0287). We conclude that DRD2/DARPP-32 expression is associated with tumor progression and that DRD2/DARPP-32 expressions may help predict prognosis in patients with ESCC.