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Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
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C-MET overexpression and amplification in gliomas
Yoonjin Kwak1, Seong-Ik Kim1, Chul-Kee Park2
1Department of Pathology, Seoul National University Hospital Seoul, Republic of Korea.
International Journal of Clinical and Experimental Pathology
|January 30, 2016
Summary
c-Met overexpression in glioblastoma multiforme (GBM) is linked to longer survival, while MET gene amplification, though rare, indicates tumor aggressiveness. MET inhibitors may benefit a subset of GBM patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- c-Met signaling pathway plays a role in tumor growth and progression.
- Dysregulation of c-Met, including overexpression and gene amplification, is implicated in various cancers.
- Gliomas are primary brain tumors with varying grades of malignancy.
Purpose of the Study:
- To determine the incidence of c-Met overexpression and MET gene amplification in gliomas.
- To investigate the prognostic significance of c-Met overexpression and MET gene amplification in glioblastoma.
- To assess the association of MET alterations with glioma grade and aggressiveness.
Main Methods:
- Tissue microarrays from 250 glioma patients (137 GBM, 113 grade II/III) were analyzed.
- Immunohistochemistry was used to detect c-Met protein overexpression.
- Fluorescence in situ hybridization (FISH) was performed to identify MET gene amplification.
Main Results:
- c-Met overexpression was found in 13.1% of GBMs, and MET gene amplification in 5.1%.
- All MET-amplified GBMs showed c-Met overexpression, but not vice versa.
- No c-Met overexpression or MET amplification was observed in grade II/III gliomas.
- GBM patients with c-Met overexpression had significantly longer survival (P=0.035).
- MET amplification was not linked to survival but was associated with higher glioma grade (only in GBM).
Conclusions:
- c-Met overexpression is a favorable prognostic marker in glioblastoma.
- MET gene amplification is a marker of aggressiveness, restricted to high-grade gliomas (GBM).
- MET inhibitor therapy could be a potential treatment strategy for approximately 5% of GBM patients with MET amplification.
