Related Experiment Video
Updated: Mar 11, 2026
Serum and Plasma Copy Number Detection Using Real-time PCR
Published on: December 15, 2017
MET expression and copy number status in clear-cell renal cell carcinoma: prognostic value and potential predictive
Stephan Macher-Goeppinger1,2,3, Martina Keith1,2, Volker Endris1
1Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Abstract:
Multiple targeted therapy for advanced clear-cell renal cell carcinoma (RCC) has substantially improved patient outcome, but complete remission is uncommon and many tumors eventually develop resistance. Mechanistic, preclinical, and early clinical data highlight c-Met / hepatocyte growth factor receptor as a promising target for RCC therapeutic agents.We have examined MET expression, frequency of MET gene copy gains and MET gene mutation in a large, hospital-based series of renal cell carcinomas with long-term follow-up information.Out of a total of 572 clear-cell RCC, only 17% were negative for MET expression whereas 32% showed high protein levels. High MET expression and MET copy number gains were associated with an aggressive phenotype and an unfavorable patient outcome. Elevated protein levels in absence of gene amplification were not attributed to mutations, based on results of targeted next-generation sequencing.Our data reveal that clear-cell RCC with MET upregulation show an aggressive behavior and MET copy number increase is evident in a substantial percentage of patients with high-grade carcinomas and metastatic disease. Diagnostic assessment of MET expression and amplification may be of predictive value to guide targeted therapy against MET signaling in patients with clear-cell RCC.
Insights
High MET expression and gene copy gains in clear-cell renal cell carcinoma (RCC) correlate with aggressive disease and poor outcomes. Assessing MET status may guide targeted therapies for advanced RCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapies have improved outcomes for advanced clear-cell renal cell carcinoma (RCC), but resistance remains a challenge.
- The c-Met receptor tyrosine kinase is a potential therapeutic target in RCC.
- Understanding MET alterations is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate the expression levels, gene copy number variations, and mutations of MET in a large cohort of clear-cell RCC.
- To correlate MET status with clinicopathological features and patient outcomes.
- To evaluate the potential of MET as a predictive biomarker for targeted therapy.
Main Methods:
- Retrospective analysis of 572 clear-cell RCC cases with long-term follow-up.
- Assessment of MET protein expression via immunohistochemistry.
- Analysis of MET gene copy number gains using fluorescence in situ hybridization (FISH).
- Targeted next-generation sequencing to detect MET mutations.
Main Results:
- 17% of RCC cases lacked MET expression, while 32% exhibited high protein levels.
- High MET expression and increased MET gene copy numbers were significantly associated with an aggressive tumor phenotype and unfavorable patient prognosis.
- Elevated MET protein levels, in the absence of gene amplification, were not linked to MET mutations.
Conclusions:
- MET upregulation and gene copy gains are prevalent in aggressive clear-cell RCC, particularly in high-grade and metastatic disease.
- MET status (expression and amplification) may serve as a predictive biomarker for guiding MET-targeted therapies in RCC patients.
- Further validation is needed to integrate MET assessment into clinical decision-making for RCC treatment.
More Related Videos
12:22The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
09:32Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
