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. Cancer 2008. © 2007 American Cancer Society.

Prognostic implication of MET overexpression in myxofibrosarcomas: an integrative array comparative genomic hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemical analysis

“…51 Conversely, MET overexpression was frequently found in skull base chordomas, but significantly predictive of favorable prognosis. 50 In primary myxofibrosarcomas, we have identified for the first time that MET overexpression was independently predictive of shorter OS and MeFS as well as being associated with tumor size and mitotic rate. Our findings and the reported discrepancies in the implications of MET expression among various sarcoma types indicated its pleiotropic functions in tumor development, progression, and dissemination.…”

Analysis of the fibroblastic growth factor receptor-RAS/RAF/MEK/ERK-ETS2/brachyury signalling pathway in chordomas

“…As it is known that chordomas also express several other tyrosine kinase receptors including c-MET, PDGFR b and KIT, EGFR, Her2/ neu and TrK, which also activate the RAS/RAF/ MEK/ERK pathway, these should be considered candidates for the regulation of brachyury. [28][29][30][31][32] The occurrence of FGFR mutations is well documented in the literature, and these are associated in both neoplasia and developmental syndromes. The mutations implicated in the former include those in endometrial, gastric, urothelial and prostatic cancers, 21,[33][34][35][36][37] and many of the activating FGFR2 and FGFR3 mutations, recently reported in endometrial carcinomas, are identical to germline mutations known to cause syndromes, several of which give rise to skeletal abnormalities including the Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and the SAD-DAN syndrome (see Supplementary Table 2 based on Catalogue of Somatic Mutations In Cancer (COSMIC).…”

The molecular aspects of chordoma

“…Urokinase plasminogen activator (uPA) expression was also found to be associated with a higher c-MET expression in primary lesions; however, in recurrent lesions, a higher c-MET expression was found to be related to the scores of uPA, MMP-1, MMP-2, and the tissue inhibitor of matrix metalloproteinase-1. Patients who had a higher c-MET expression had longer survival times [63].…”