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

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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Targeted Oncology, Springer Verlag (Germany), 2017, 12 (4), pp.487-494. 〈10.1007/s11523-017-0498-1〉
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Solène-Florence Kammerer-Jacquet, Sarah Médane, Karim Bensalah, Jean-Christophe Bernhard, Mokrane Yacoub, et al.. Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy. Targeted Oncology, Springer Verlag (Germany), 2017, 12 (4), pp.487-494. 〈10.1007/s11523-017-0498-1〉. 〈hal-01578072〉

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