Loss of Raf-1 kinase inhibitory protein in pancreatic ductal adenocarcinoma

Aims: Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers. The aim of this study was to evaluate RKIP expression and to determine its association with metastasis and prognostic significance in pancreatic cancer patients. Methods: Immunohistochemical staining for RKIP was performed on 63 cases of pancreatic ductal adenocarcinoma (PDAC). We investigated whether RKIP expression correlated with clinicopathological parameters and patient outcomes. Results: The islet cells, acinar cells and ductal epithelial cells of normal pancreas consistently showed strong RKIP immunoreactivity. In contrast, in PDAC, RKIP was lost in 57.1% (37/63) of cases. Loss of RKIP expression was significantly associated with the presence of nodal (p=0.001) and distant (p=0.010) metastases and a higher stage group (p=0.012). Univariate analysis for distant metastasis-free survival (DMFS) showed that the median DMFS of RKIP negative PDAC patients (10 months) was significantly shorter than that of RKIP positive PDAC patients (17 months; p=0.009). Multivariate analysis also revealed that loss of RKIP expression was an independent predictor of worse DMFS in PDAC patients (p=0.015). Conclusions: Our results strongly suggest that RKIP is a metastasis suppressor in PDAC.