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

SummaryAimsRaf-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.MethodsImmunohistochemical 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.ResultsThe 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).ConclusionsOur results strongly suggest that RKIP is a metastasis suppressor in PDAC.