Expression of Raf-1 kinase inhibitory protein in carcinoma of the ampulla of Vater

Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human malignancies. We have recently demonstrated that reduced expression of RKIP is significantly associated with invasion and metastasis in periampullary carcinomas, including pancreatic carcinoma, gallbladder carcinoma, and extrahepatic bile duct carcinoma. In this study, we evaluated RKIP expression in ampulla of Vater (AoV) carcinoma and investigated its prognostic significance. Immunostaining for RKIP was performed for 80 and 21 cases with primary and nodal metastatic AoV carcinoma, respectively. RKIP expression was reduced in 32.5% (26/80) and 66.7% (14/21) of primary and nodal metastatic AoV carcinoma cases, respectively. This distribution of RKIP expression was statistically significant (P<0.001). The reduction in RKIP expression was significantly associated with the presence of nodal (P=0.008) and distant (P=0.002) metastases, a higher TNM stage group (P=0.010), lymphatic invasion (P<0.001), vascular invasion (P<0.001), and a shorter disease-free survival (DFS; P= 0.028) and distant metastasis-free survival (DMFS; P= 0.005). In addition, reduced RKIP expression was an independent prognostic predictor for worse DFS and DMFS (P=0.032 and P=0.036, respectively). Our data suggest that a reduction in RKIP expression contributes to invasion and metastasis in AoV carcinoma and is a significant prognostic marker in patients with AoV carcinoma.