CD40 Expression in Human Esophageal Squamous Cell Carcinoma Is Associated with Tumor Progression and Lymph Node Metastasis

The co-stimulatory molecule cluster of differentiation 40 (CD40) is widely expressed in various types of malignant tumors, but its role remains unclear. The purpose of this study was to investigate the relationship between CD40 expression and clinicopathological variables in patients with esophageal squamous cell carcinoma (ESCC), as well as the function of CD40 expressed on ESCC tumor cells in vitro. Tumor specimens of patients who underwent surgical resection for ESCC were immunohistochemically analyzed for CD40 expression. Of the 122 specimens, 45 (37%) were positive for CD40. Significant positive correlation was found between CD40 expression and p-stage (p=0.0011), histopathological grade (p=0.0143), pT-classification (p=0.0011), and pN-classification (p=0.0007). Survival of patients with stage III and IV disease with positive CD40 expression was significantly shorter than that of those with negative expression (log-rank test, p=0.0422). In in vitro analysis, while the addition of recombinant human CD154 did not inhibit growth, it did induce a significant increase in interleukin 6 production in ESCC cell lines. These results suggest that functional expression of CD40 on tumor cells might play an important role in tumor progression and lymph node metastasis in ESCC.