Expression of CD40 and COX-2 and its relationship with angiogenesis in esophageal squamous cell carcinoma

Objective: To explore the putative role of CD40 and COX-2 expression in human esophageal squamous cell carcinoma (ESCC) and to analyze their possible relationship with angiogenesis in ESCC. Methods: The expression of CD40 and COX-2 was detected in 79 ESCC and 28 normal esophageal epithelial tissue samples with immunohistochemical staining. The microvessel density by CD34 was determined and the clinicopathological significance of CD40 and COX-2 expression in ESCC was analyzed. In addition, the expression of CD40 and COX-2 in esophageal squamous cell carcinoma cell line Eca109 and primary cultured normal esophageal epithelial cells in vivo was comparatively studied with immunocytochemical staining and Western blot. Results: Compared with that in normal epithelial tissues, the expression of CD40 and COX-2 in ESCC was significantly higher (54.43% vs 10.71%; 69.62% vs 17.86%; respectively, P<0.05). The positive expression rate of CD40 in ESCC cases with lymph node metastasis was significantly higher than that in those without lymph node metastasis (70.37% vs 46.15%, P<0.05). No correlation was found between CD40 expression and patient age, sex, tumor location, size and differentiation of tumors. No clinicopathological significance of COX-2 expression in ESCC was found. There was a positive correlation between CD40 expression and COX-2 expression in esophageal squamous cell carcinoma (P<0.05, Φ=0.446). The mean MVD value in ESCC was significantly higher than that in normal esophageal tissue (25.02±5.52 vs 12.09±4.55, P<0.05). MVD value in ESCC was closely correlated with lymph node metastasis. The mean MVD value in ESCC cases with positive CD40 and COX-2 expression was higher than that in those with negative CD40 and COX-2 expression (26.37±6.02 vs 22.58±5.25, P<0.05). Western blot results showed that CD40 and COX-2 expression in Eca109 was higher than that in cultured normal esophageal epithelial cells (P<0.05). Conclusion: The expression of CD40 is involved in the carcinogenesis and progression of esophageal squamous cell carcinoma. CD40 may play an important role in the angiogenesis of ESCC through promoting COX-2 expression.