title: Expression level of vascular endothelial growth factor receptor-2 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with sunitinib.
abstract: OBJECTIVE
  To investigate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) treated with sunitinib in order to identify factors predicting susceptibility to this agent.
  
  
  METHODS
  This study included a total of 40 consecutive patients undergoing radical nephrectomy, who were diagnosed as having metastatic RCC and subsequently treated with sunitinib. Expression levels of 10 molecular markers, including Bcl-2, Bcl-xL, Bax, phosphorylated Akt, p44/42 mitogen-activated protein kinase, and signal transducers and activation of transcription 3, vascular endothelial growth factor receptor (VEGFR)-1 and -2, and platelet-derived growth factor receptor-α and -β, in primary RCC specimens were assessed by immunohistochemical staining.
  
  
  RESULTS
  Of several factors examined, tumor grade and the expression level of VEGFR-2 were shown to have significant impacts on response to sunitinib in these 40 patients. Progression-free survival (PFS) was significantly associated with the expression levels of VEGFR-2 in addition to tumor grade, performance status, Memorial Sloan-Kettering Cancer Center risk classification and pretreatment c-reactive protein level on univariate analysis. Of these significant factors, only VEGFR-2 expression appeared to be independently related to PFS on multivariate analysis. In fact, PFS in patients with strong expression of VEGFR-2 was significantly favorable compared with that in those with weak expression of VEGFR-2.
  
  
  CONCLUSIONS
  Collectively, these findings suggest that it would be useful to consider expression levels of potential molecular markers, particularly VEGFR-2, as well as conventional clinical parameters to select metastatic RCC patients likely to benefit from treatment with sunitinib.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Terakawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kusuda
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000401:mortality*; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib