Expression of hepatocyte growth factor and c-MET in skull base chordoma.

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.

• Authors: Takahiko Naka, Doerthe Kuester, Carsten Boltze, Stefanie Scheil-Bertram, Amir Samii, Christian Herold, Helmut Ostertag, Sabine Krueger, Albert Roessner
• Journal: Cancer (Cancer) Vol. 112 Issue 1 Pg. 104-10 (Jan 01 2008) ISSN: 0008-543X [Print] United States
• PMID: 17948912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor (metabolism)
• Cell Differentiation
• Cell Proliferation
• Child
• Chordoma (metabolism, pathology, therapy)
• Female
• Hepatocyte Growth Factor (metabolism)
• Humans
• Male
• Middle Aged
• Neoplasm Invasiveness
• Prognosis
• Proto-Oncogene Proteins c-met (metabolism)
• Skull Base Neoplasms (metabolism, pathology, therapy)