Immunohistochemical analysis of cyclooxygenase-2 and vascular endothelial growth factor in pancreaticobiliary maljunction

Recent studies have elucidated that cyclooxygenase (COX)-2 is strongly related to cancer progression or development by means of its anti-apoptotic effect, enhancement of angiogenesis or decrease of cell-to-cell adhesive activity. However, there is no report on the relationship between COX-2 expression and angiogenesis in pancreaticobiliary maljunction (PBM). We examined the correlation between the overexpression of COX-2 and vascular endothelial growth factor (VEGF) in 65 lesions from 30 patients with PBM immunohistochemically. The positive expression of COX-2 was found in 20% of regenerative epithelium, 11.1% of hyperplasia without atypia, 86.4% of hyperplasia with mild atypia, 75% of dysplasia, and 75% of cancerous lesions. VEGF was highly expressed in 80% of regenerative epithelium, 27.8% of hyperplasia without atypia, 86.4% of hyperplasia with mild atypia, 66.7% of dysplasia, and 75% of cancerous lesions. The positive rate of both COX-2 and VEFG expression was significantly higher in hyperplasia with atypia, dysplasia and cancerous lesions than that in hyperplasia without atypia. In addition, there was a statistically significant correlation between COX-2 and VEGF overexpression among all lesions. In 6 of 8 patients of various histological types, both COX-2 and VEGF were stained in almost exactly the same locations. In addition, there were no significant differences between the degree of inflammatory cell infiltration in the surrounding stroma and the expression of COX-2 and VEGF, respectively. These results demonstrated a strong relationship between COX-2 and VEGF overexpression in PBM. Therefore, chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be effective in PBM.