title: Loss of Raf-1 kinase inhibitory protein in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein