title: Microvessel area as a predictor of sorafenib response in metastatic renal cell carcinoma.
abstract: BACKGROUND
  Sorafenib was the first Food and Drug Administration approved anti-angiogenic therapy for renal cell carcinoma (RCC). Currently, there are no validated predictive biomarkers for sorafenib. Our purpose was to determine if sorafenib target expression is predictive of sorafenib sensitivity.
  
  
  METHODS
  We used an automated, quantitative immunofluorescence-based method to determine expression levels of sorafenib targets VEGF, VEGF-R1, VEGF-R2, VEGF-R3, c-RAF, B-RAF, c-Kit, and PDGFR-β in a cohort of 96 patients treated with sorafenib. To measure vasculature in the tumor samples, we measured microvessel area (MVA) by CD-34 staining.
  
  
  RESULTS
  Of the markers studied, only high MVA was predictive of response (p = 0.005). High MVA was associated with smaller primary tumors (p = 0.005). None of the biomarkers studied was predictive of overall or progression-free survival. Using the Bonferroni adjustment correcting for 9 variables with an alpha of 0.05, MVA remained significantly associated with sorafenib response.
  
  
  CONCLUSIONS
  Our results suggest that high MVA in tumor specimens might be associated with a greater likelihood of response to therapy. Further studies are needed to confirm these results in additional patients and in patients receiving other VEGF-R2 inhibitors, as MVA might be useful to improve patient selection for VEGF-R2 inhibitors.
authors.affiliation: Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA.
authors.forename: Saadia A
authors.initials: SA
authors.lastname: Aziz
authors.affiliation: Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sznol
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Zito
authors.affiliation: Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA.
authors.forename: Lucia B
authors.initials: LB
authors.lastname: Jilaveanu
authors.affiliation: Departments of Medicine and Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA.
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger