PMID- 28550387 OWN - NLM STAT- MEDLINE DCOM- 20180504 LR - 20181202 IS - 1776-260X (Electronic) IS - 1776-2596 (Linking) VI - 12 IP - 4 DP - 2017 Aug TI - Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy. PG - 487-494 LID - 10.1007/s11523-017-0498-1 [doi] AB - 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. FAU - Kammerer-Jacquet, Solene-Florence AU - Kammerer-Jacquet SF AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service d'Anatomie et Cytologie Pathologiques, F-35042, Rennes, France. jacquet.sf@gmail.com. FAU - Medane, Sarah AU - Medane S AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service d'Anatomie et Cytologie Pathologiques, F-35042, Rennes, France. FAU - Bensalah, Karim AU - Bensalah K AD - Universite de Rennes 1, CHU de Rennes, Service d'Urologie, F-35042, Rennes, France. FAU - Bernhard, Jean-Christophe AU - Bernhard JC AD - Service d'Urologie, CHU Pellegrin, Bordeaux, France. FAU - Yacoub, Mokrane AU - Yacoub M AD - Service d'Anatomie et Cytologie Pathologiques, CHU Pellegrin, Bordeaux, France. FAU - Dupuis, Frantz AU - Dupuis F AD - Service d'Anatomie et Cytologie Pathologiques, CHU Pellegrin, Bordeaux, France. FAU - Ravaud, Alain AU - Ravaud A AD - Service d'Oncologie Medicale, CHU Saint-Andre, Bordeaux, France. FAU - Verhoest, Gregory AU - Verhoest G AD - Universite de Rennes 1, CHU de Rennes, Service d'Urologie, F-35042, Rennes, France. FAU - Mathieu, Romain AU - Mathieu R AD - Universite de Rennes 1, CHU de Rennes, Service d'Urologie, F-35042, Rennes, France. FAU - Peyronnet, Benoit AU - Peyronnet B AD - Universite de Rennes 1, CHU de Rennes, Service d'Urologie, F-35042, Rennes, France. FAU - Brunot, Angelique AU - Brunot A AD - Centre Eugene Marquis, Service d'Oncologie Medicale, Universite de Rennes 1, Rennes, France. FAU - Laguerre, Brigitte AU - Laguerre B AD - Centre Eugene Marquis, Service d'Oncologie Medicale, Universite de Rennes 1, Rennes, France. FAU - Lespagnol, Alexandra AU - Lespagnol A AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service de Genetique Somatique des Cancers, F-35042, Rennes, France. FAU - Mosser, Jean AU - Mosser J AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service de Genetique Somatique des Cancers, F-35042, Rennes, France. FAU - Dugay, Frederic AU - Dugay F AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service de Cytogenetique et Biologie cellulaire, F-35042, Rennes, France. FAU - Belaud-Rotureau, Marc-Antoine AU - Belaud-Rotureau MA AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service de Cytogenetique et Biologie cellulaire, F-35042, Rennes, France. FAU - Rioux-Leclercq, Nathalie AU - Rioux-Leclercq N AD - Universite de Rennes 1, UMR 6290-IGDR, Univ Bretagne Loire, CHU de Rennes, Service d'Anatomie et Cytologie Pathologiques, F-35042, Rennes, France. LA - eng PT - Journal Article PL - France TA - Target Oncol JT - Targeted oncology JID - 101270595 RN - 0 (Antineoplastic Agents) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (Indoles) RN - 0 (Pyrroles) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - V99T50803M (Sunitinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*therapeutic use MH - B7-H1 Antigen/*biosynthesis/metabolism MH - Carcinoma, Renal Cell/drug therapy/genetics/*metabolism/pathology MH - Female MH - Gene Dosage MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Indoles/*therapeutic use MH - Male MH - Middle Aged MH - Prognosis MH - Proto-Oncogene Proteins c-met/*biosynthesis/genetics/metabolism MH - Pyrroles/*therapeutic use MH - Sunitinib EDAT- 2017/05/28 06:00 MHDA- 2018/05/05 06:00 CRDT- 2017/05/28 06:00 PHST- 2017/05/28 06:00 [pubmed] PHST- 2018/05/05 06:00 [medline] PHST- 2017/05/28 06:00 [entrez] AID - 10.1007/s11523-017-0498-1 [pii] AID - 10.1007/s11523-017-0498-1 [doi] PST - ppublish SO - Target Oncol. 2017 Aug;12(4):487-494. doi: 10.1007/s11523-017-0498-1.