Oncotarget

Research Papers:

MET expression and copy number status in clear-cell renal cell carcinoma: prognostic value and potential predictive marker

Stephan Macher-Goeppinger _, Martina Keith, Volker Endris, Roland Penzel, Katrin E. Tagscherer, Sascha Pahernik, Markus Hohenfellner, Humphrey Gardner, Carsten Grüllich, Peter Schirmacher and Wilfried Roth

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Oncotarget. 2017; 8:1046-1057. https://doi.org/10.18632/oncotarget.13540

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Abstract

Stephan Macher-Goeppinger1,2,3, Martina Keith1,2, Volker Endris1, Roland Penzel1, Katrin E. Tagscherer1,2, Sascha Pahernik4, Markus Hohenfellner4, Humphrey Gardner5, Carsten Grüllich6, Peter Schirmacher1, Wilfried Roth1,2,3

1Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany

2Molecular Tumor Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

3Institute of Pathology, University Medical Center Mainz, Mainz, Germany

4Department of Urology, University Hospital Heidelberg, Heidelberg, Germany

5Translational Medicine, Early Clinical Development, AstraZeneca, Gatehouse Park, Waltham, MA, USA

6Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, University Hospital Heidelberg, Heidelberg, Germany

Correspondence to:

Stephan Macher-Goeppinger, email: [email protected]

Keywords: renal cell carcinoma, MET, HGF, targeted therapy, biomarker

Received: June 07, 2016    Accepted: November 07, 2016    Published: November 24, 2016

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.


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