title: Reduced Raf-1 kinase inhibitor protein expression predicts less favorable             outcomes in patients with hepatic colorectal metastasis.
abstract: Reduced expression of Raf-1 kinase inhibitor protein (RKIP) has been documented             in a number of human malignancies, including colorectal carcinoma (CRC). However,             despite the importance of hepatic colorectal metastasis (HCM) for the prognosis             of CRC patients, no studies have been conducted regarding RKIP expression in HCM             tissues or its prognostic significance. The aim of this study was to clarify the             relationship between reduced RKIP expression and HCM and to identify independent             predictors for recurrent HCM, which will ultimately help identify patients at             high risk of developing metastatic recurrence. An immunohistochemical study of             RKIP expression was performed using primary CRC and/or corresponding HCM tissue             samples obtained from 117 patients. Forty-nine of these patients did not harbor             HCM and 68 harbored HCM. RKIP expression was reduced in 24.5% (12/49) of CRCs             without HCM, 47.1% (32/68) of CRCs with HCM and 67.6% (46/68) of HCM. This distribution             of RKIP downregulation was statistically significant. RKIP expression was found             to independently predict recurrent HCM, with a higher relative risk (6.661) compared             to that of nodal metastasis (4.690). A reduction of RKIP expression in HCM was             a significant predictor of poor prognosis. The median survival of patients with             reduced RKIP expression was 35 months, compared with more than 10 years in patients             with positive RKIP expression. Multivariate survival analysis demonstrated that             RKIP expression in HCM was an independent predictor of overall survival, with             a hazard ratio of 5.161, a value comparable to the risk associated with advanced             TNM stage (5.247). We demonstrated that a reduction of RKIP expression in HCM             had an independent predictive value for metastatic recurrence and less favorable             clinical outcomes in patients with HCM. Our results strongly suggest that patients             harboring HCM with reduced RKIP expression require careful monitoring after hepatic             resection to detect potentially resectable metastatic recurrences.
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: Sun Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Kil Yeon
authors.initials: KY
authors.lastname: Lee
authors.forename: Yong-Koo
authors.initials: YK
authors.lastname: Park
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein