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26.05.2017 | Original Research Article

Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy

verfasst von: Solène-Florence Kammerer-Jacquet, Sarah Medane, Karim Bensalah, Jean-Christophe Bernhard, Mokrane Yacoub, Frantz Dupuis, Alain Ravaud, Grégory Verhoest, Romain Mathieu, Benoit Peyronnet, Angélique Brunot, Brigitte Laguerre, Alexandra Lespagnol, Jean Mosser, Frédéric Dugay, Marc-Antoine Belaud-Rotureau, Nathalie Rioux-Leclercq

Erschienen in: Targeted Oncology | Ausgabe 4/2017

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Abstract

Background

Clear cell renal cell carcinoma (ccRCC) is highly metastatic. Cabozantinib, an anti-angiogenic tyrosine kinase inhibitor that targets c-MET, provided interesting results in metastatic ccRCC treatment.

Objective

To understand better the role of c-MET in ccRCC, we assessed its status in a population of patients with metastatic ccRCC.

Patients and Methods

For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib. The expression of c-MET was correlated with pathological, immunohistochemical (VEGFA, CAIX, PD-L1), clinical, and molecular criteria (VHL status) by univariate and multivariate analyses and to clinical outcome using Kaplan-Meier curves compared by log-rank test.

Results

Of ccRCC, 31.1% had low c-MET expression (absent to weak intensity by IHC) versus 68.9% with high expression (moderate to strong intensity). High expression of c-MET was associated with a gain in FISH analysis (p=0.0284) without amplification. No mutations were detected in NGS. Moreover, high c-MET expression was associated with lymph node metastases (p=0.004), sarcomatoid component (p=0.029), VEGFA (p=0.037), and PD-L1 (p=0.001) overexpression, the only factor that remained independently associated (p<0.001) after logistic regression. No difference was observed in clinical outcomes.

Conclusion

This study is the first to analyse c-MET status in metastatic ccRCC. The high expression of c-MET in the majority of ccRCC and its independent association with PD-L1 expression, may suggest a potential benefit from combining c-MET inhibitors and targeted immunotherapy.

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Titel: Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy
verfasst von: Solène-Florence Kammerer-Jacquet
Sarah Medane
Karim Bensalah
Jean-Christophe Bernhard
Mokrane Yacoub
Frantz Dupuis
Alain Ravaud
Grégory Verhoest
Romain Mathieu
Benoit Peyronnet
Angélique Brunot
Brigitte Laguerre
Alexandra Lespagnol
Jean Mosser
Frédéric Dugay
Marc-Antoine Belaud-Rotureau
Nathalie Rioux-Leclercq
Publikationsdatum: 26.05.2017
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 4/2017
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-017-0498-1

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Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy