title: Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma.
abstract: BACKGROUND
  Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC), but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status, vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression, and their relationships with characteristics and clinical outcome of advanced ccRCC.
  
  
  METHODS
  A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Parafﬁn-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and overall survival (OS) were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses.
  
  
  RESULTS
  Of 59 patients, objective responses were observed in 28 patients (47.5%). The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6%) had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%). VHL mutation status did not correlate with either overall response rate (P = 0.938) or PFS (P = 0.277). The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043).
  
  
  CONCLUSIONS
  VHL mutation status could not predict the efficacy of sunitinib or pazopanib. Further investigation of VHL/VEGFR pathway components is needed.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Medical Oncology, Cancer Hospital (Institute), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Shan
authors.forename: Hong-Tu
authors.initials: HT
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; C516667:pazopanib; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000077210:Sunitinib