Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer.

Abstract

Raf-1 kinase inhibitor protein (RKIP) is known as a critical down-regulator of the mitogen-activated protein kinase signaling pathway and a potential molecular determinant of malignant metastasis. The aim of this study was to determine the prognostic significance of RKIP expression in colorectal cancer (CRC). Immunohistochemical staining for RKIP was performed on a tissue microarray comprising 1,197 mismatch repair (MMR)-proficient and 141 MMRdeficient CRCs. The association of RKIP with clinicopathologic features was analyzed. Loss of cytoplasmic RKIP was associated with distant metastasis (P = .038), higher N stage (P = .032), vascular invasion (P = .01), and worse survival (P = .001) in the MMR-proficient group. In MMR-deficient CRCs, loss of cytoplasmic RKIP was associated with distant metastasis (P = .043) and independently predicted worse survival (P = .004). Methylation analysis of 28 cases showed that loss of RKIP expression is unlikely to be due to promoter methylation.Loss of RKIP expression is a marker of tumor progression and distant metastasis in MMR-proficient and MMR-deficient CRCs.

• Authors: Parham Minoo, Inti Zlobec, Kristi Baker, Luigi Tornillo, Luigi Terracciano, Jeremy R Jass, Alessandro Lugli
• Journal: American journal of clinical pathology (Am J Clin Pathol) Vol. 127 Issue 5 Pg. 820-7 (May 2007) ISSN: 0002-9173 [Print] England
• PMID: 17439843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• PEBP1 protein, human
• Phosphatidylethanolamine Binding Protein

Topics

• Colorectal Neoplasms (chemistry, genetics, mortality, pathology)
• DNA Methylation
• DNA Mismatch Repair
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Male
• Neoplasm Metastasis
• Phosphatidylethanolamine Binding Protein (analysis, genetics)
• Promoter Regions, Genetic
• ROC Curve