Abstract
BACKGROUND.
Hepatocyte growth factor (HGF) is a multipotent cytokine that is mediated by its receptor, cโMET. HGF/cโMET contributes to tumor progression in many human malignancies; however, HGF/cโMET is inversely correlated with aggressive biologic behavior in other cancers. Conversely, to the authors' knowledge, little is known regarding the significance of HGF/cโMET expression in skull base chordoma.
METHODS.
Using immunohistochemical techniques, the authors investigated HGF/cโMET 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.
cโMET was found to be expressed in 70.0% of primary and 88.0% of recurrent lesions. HGF expression was scarcely detected. Higher cโMET 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 cโMET scores in both primary and recurrent lesions compared with those with lower CAM5.2 expression. In recurrent lesions, higher cโMET expression was found to be associated with the scores of matrix metalloproteinase (MMP)โ1, MMPโ2, tissue inhibitor of matrix metalloproteinaseโ1, and urokinase plasminogen activator (uPA); however, only uPA was found to be correlated with higher cโMET expression in primary lesions. cโMET expression did not appear to be correlated with MIBโ1 labeling index. Patients with higher cโMET expression were found to have longer survival.
CONCLUSIONS.
In the current study, cโMET 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/cโMET paracrine signaling also may contribute to its invasive ability, especially in recurrent lesions. Cancer 2008. ยฉ 2007 American Cancer Society.