title: 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.affiliation: Department of Pathology, Faculty of Medicine, Magdeburg University, Magdeburg, Germany. takahicom@hotmail.com
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naka
authors.forename: Doerthe
authors.initials: D
authors.lastname: Kuester
authors.forename: Carsten
authors.initials: C
authors.lastname: Boltze
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scheil-Bertram
authors.forename: Amir
authors.initials: A
authors.lastname: Samii
authors.forename: Christian
authors.initials: C
authors.lastname: Herold
authors.forename: Helmut
authors.initials: H
authors.lastname: Ostertag
authors.forename: Sabine
authors.initials: S
authors.lastname: Krueger
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met