Expression of hepatocyte growth factor and c-MET in skull base chordoma.
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.
Naka
Takahiko
T
Department of Pathology, Faculty of Medicine, Magdeburg University, Magdeburg, Germany. takahicom@hotmail.com
Kuester
Doerthe
D
Boltze
Carsten
C
Scheil-Bertram
Stefanie
S
Samii
Amir
A
Herold
Christian
C
Ostertag
Helmut
H
Krueger
Sabine
S
Roessner
Albert
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D002817:Chordoma / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D019292:Skull Base Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy
D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met