title: Correlation of c-Met Expression and Outcome in Patients With Renal Cell Carcinoma Treated With Sunitinib.
abstract: Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinib-treated patients with mRCC, including patients with bone metastases.
  
  
  
  c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol.
  
  
  
  Patients with low c-Met expression (n = 78) had longer progression-free survival (PFS) (median 14.3 vs. 6.5 months; P < .001) and overall survival (OS) (median 32.1 vs. 20.1 months; P = .049) than those with high expression. High c-Met expression was an independent predictor of unfavorable PFS in a Cox proportional hazards model adjusted for the Heng risk criteria (HR 1.60 [1.09-2.35]; P = .016). In a subgroup of patients with no bone metastases (n = 106), low c-Met expression was associated with a both longer OS (unadjusted HR 0.63 [95% CI, 0.42-0.95]; P = .034) and PFS (unadjusted HR 0.47 [95% CI, 0.31-0.71]; P < .001).
  
  
  
  High c-Met expression was associated with poor survival in patients with mRCC treated with sunitinib. Interestingly, the prognostic role may vary based on the location of metastases.
authors.affiliation: Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Katriina Johanna
authors.initials: KJ
authors.lastname: Peltola
authors.affiliation: Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Penttilä
authors.affiliation: Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Juhana
authors.initials: J
authors.lastname: Rautiola
authors.affiliation: Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.affiliation: Pathology, Research Programs Unit and HUSLAB, University of Helsinki, Helsinki, Finland.
authors.forename: Erkki
authors.initials: E
authors.lastname: Hänninen
authors.affiliation: Pathology, Research Programs Unit and HUSLAB, University of Helsinki, Helsinki, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Ristimäki
authors.affiliation: Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland. Electronic address: petri.bono@hus.fi.
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011758:Pyrroles; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D000077210:Sunitinib
keywords: Angiogenesis inhibitor; Prognostic marker; c-Met inhibitor; mRCC