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Dr. Naka was supported by grants from Uehara Memorial Foundation, Japan.
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Original Article
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Expression of hepatocyte growth factor and c-MET in skull base chordoma
Article first published online: 19 OCT 2007
DOI: 10.1002/cncr.23141
Copyright © 2007 American Cancer Society
Additional Information
How to Cite
Naka, T., Kuester, D., Boltze, C., Scheil-Bertram, S., Samii, A., Herold, C., Ostertag, H., Krueger, S. and Roessner, A. (2008), Expression of hepatocyte growth factor and c-MET in skull base chordoma. Cancer, 112: 104–110. doi: 10.1002/cncr.23141
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Dr. Naka was supported by grants from Uehara Memorial Foundation, Japan.
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Dr. Scheil-Bertram was supported by grants from the Deutsche Krebshilfe e.V. (German Cancer Aid), Germany.
Publication History
- Issue published online: 17 DEC 2007
- Article first published online: 19 OCT 2007
- Manuscript Accepted: 9 AUG 2007
- Manuscript Revised: 2 AUG 2007
- Manuscript Received: 20 JUN 2007
- Abstract
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Keywords:
- chordoma;
- hepatocyte growth factor;
- c-MET;
- epithelial differentiation;
- proteinase;
- invasion;
- proliferation;
- prognosis
Abstract
BACKGROUND.
Hepatocyte growth factor (HGF) is a multipotent cytokine that is mediated by its receptor, c-MET. HGF/c-MET contributes to tumor progression in many human malignancies; however, HGF/c-MET is inversely correlated with aggressive biologic behavior in other cancers. Conversely, to the authors' knowledge, little is known regarding the significance of HGF/c-MET expression in skull base chordoma.
METHODS.
Using immunohistochemical techniques, the authors investigated HGF/c-MET expression in 46 primary and 25 recurrent lesions, and compared it with the expression of proteinases and cell differentiation markers, proliferative ability, and other clinicopathologic parameters.
RESULTS.
c-MET was found to be expressed in 70.0% of primary and 88.0% of recurrent lesions. HGF expression was scarcely detected. Higher c-MET expression was found to be correlated with younger patient age. Lesions with a higher expression of low molecular weight cytokeratin (CAM5.2) demonstrated significantly higher c-MET scores in both primary and recurrent lesions compared with those with lower CAM5.2 expression. In recurrent lesions, higher c-MET expression was found to be associated with the scores of matrix metalloproteinase (MMP)-1, MMP-2, tissue inhibitor of matrix metalloproteinase-1, and urokinase plasminogen activator (uPA); however, only uPA was found to be correlated with higher c-MET expression in primary lesions. c-MET expression did not appear to be correlated with MIB-1 labeling index. Patients with higher c-MET expression were found to have longer survival.
CONCLUSIONS.
In the current study, c-MET expression was a common event, and was found to be correlated with CAM5.2 expression, younger patient age, and a favorable prognosis in patients with skull base chordoma. However, HGF/c-MET paracrine signaling also may contribute to its invasive ability, especially in recurrent lesions. Cancer 2008. © 2007 American Cancer Society.